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1
Ferru, Geoffroy. "Spéciation moléculaire et supramoléculaire des systèmes extractants à base de monoamides." Paris 6, 2012. http://www.theses.fr/2012PA066612.
Повний текст джерелаАнотація:
Le DEHiBA a été retenu comme extractant sélectif de l'uranium lors de la première étape du procédé GANEX, procédé ayant pour but de réaliser l'extraction groupée des actinides lors d'une seconde étape. L'objectif de ces travaux de thèse est d'améliorer la description des phases organiques de monoamides dans les alcanes après extraction de solutés. Une étude paramétrique a alors été entreprise, visant à étudier séparément l'extraction d'eau, d'acide nitrique et de nitrate d'uranyle, à l'échelle moléculaire et à l'échelle supramoléculaire. L'étude de l'organisation supramoléculaire des solutions a permis de distinguer trois régimes : Pour des concentrations d'extractant inférieures à 0,5 mol/L, les espèces monomères sont majoritaires, quel que soit le soluté extrait. Pour des concentrations comprises entre 0,5 et 1 mol/L, de petits agrégats sont formés. Après extraction d'eau et d'acide nitrique, il s'agit essentiellement de dimères. L'extraction de nitrate d'uranyle engendre la formation d'objets légèrement plus gros, contenant 2 à 4 molécules de monoamide. Pour les phases plus concentrées (supérieures à 1 mol/L), des espèces contenant 2 ou 4 molécules de monoamides se formeraient après extraction d'eau ou d'acide nitrique. Concernant l'extraction de nitrate d'uranyle, une très importante structuration des phases organiques est observée, ne permettant plus de considérer la formation d'agrégats "sphériques" bien définis. D'un point de vue moléculaire, les complexes sont peu sensibles à l'organisation de la solution : les mêmes espèces sont observées, quelles que soient la concentration de l'uranyle et d'extractant en phase organiqueThe DEHiBA was chosen as extractant for the selective recovery of uranium in the GANEX process first cycle, which aims to realise the grouped extraction of actinides in a second step. The object of this work is to improve the description of monoamide organic phases in alkanes after solutes extraction. A parametric study was undertaken to study singly water, nitric acid and uranyl nitrate extraction at the molecular and supramolecular scale. The study of the organization has allowed identifying three regimes: For extractant concentration less than 0. 5 mol/L, monomeric species are majority, whatever the solute. For extractant concentration between 0. 5 and 1 mol/L, small aggregates are formed: after water and nitric acid extraction, this is essentially dimers. Uranyl nitrate extraction generates bigger objects, containing 2 to 4 molecules of monoamide. For more concentrated phases (more than 1 mol/L), species containing 2 to 4 molecules of monoamides could be formed after water or nitric nitric extraction. Concerning uranyl nitrate extraction, an important and strong organization of the organic phase is observed, which no longer allowing considering the formation of spherical well defined aggregates. From the molecular view, complexes are not sensitive to the organization of the solution: same species are observed, whatever the concentration of uranyl and of extractant in organic phase
2
Amoudji, Amivi Eméfa Félicité. "Comportement électrochimique du cérium et du plutonium dans les milieux organiques extractants monoamides." Electronic Thesis or Diss., Montpellier, Ecole nationale supérieure de chimie, 2022. http://www.theses.fr/2022ENCM0009.
Повний текст джерелаАнотація:
Les monoamides sont étudiés depuis quelques années comme extractants alternatifs au TBP dans le procédé de retraitement du combustible irradié. Ces molécules possèdent une affinité modulable pour le plutonium(IV), selon la nature de leur chaîne alkyle et selon l’acidité. Comme le TBP, les monoamides, solvants immiscibles extraient de l’eau et de l’acide nitrique lorsqu’ils sont mis en contact avec ce dernier. L’acide nitrique étant un composé instable vis-à-vis de la radiolyse, il dismute en plusieurs composés azotés dont l’acide nitreux (HNO2) qui par sa présence pourrait entrainer la formation du couple redox HNO3/HNO2 susceptible de provoquer des réactions redox parasites et perturber le procédé. Il est donc important de connaitre la spéciation redox des actinides (An) en particulier dans la phase organique d’extraction afin d’assurer une bonne maitrise du procédé.Le comportement électrochimique du couple Ce(IV)/Ce(III) a été étudié par voltampérométrie cyclique à 25 et 40°C à une électrode de carbone vitreux dans trois N,N-dialkylamides : le DEHBA (N,N-di-(2-éthylhexyl)-n-butanamide), le DEHiBA (N,N-di-(2- éthylhexyl)-iso-butanamide) et le DEHDMBA (N,N-di-(2-éthylhexyl)-3,3- diméthyl-n-butanamide) pré-équilibrés à l’eau et à l’acide nitrique (HNO3 5M). Les résultats ont montré que le processus électrochimique du couple Ce(IV)/Ce(III) est celui d’un couple redox quasi-rapide limité par la diffusion. Cette étude préalable sur le cérium analogue chimique non radioactif du plutonium a été réalisée dans le but d’identifier la nature du système électrochimique du couple Ce(IV)/Ce(III) et les difficultés liées à la réalisation de mesures électrochimiques dans ces milieux organiques très visqueux et très peu conducteurs. Le couple redox Pu(IV)/Pu(III) a ensuite été étudié à 40°C dans le DEHBA à une électrode de carbone vitreux à différentes concentrations d’acide nitrique (0,6 M < [HNO3]org < 3,7 M). Une étude préalable de la spéciation du plutonium (IV) dans la phase organique DEHBA après extraction a révélé la formation de deux types de complexes avec les ligands DEHBA et dont la prépondérance dans le milieu organique varie avec l’acidité. Les mesures de voltampérométrie cyclique ont montré que la nature des complexes de plutonium dans le DEHBA peut avoir un impact notable sur l’électroactivité du couple redox Pu(IV)/Pu(III). Il a été observé aux faibles acidités en phase organique que le processus électrochimique du couple redox Pu(IV)/Pu(III) est celui d’un couple quasi-rapide limité par la diffusion. Aucune électroactivité du couple Pu(IV)/Pu(III) n’a été observée aux fortes acidités.Cette étude a permis de déterminer les caractéristiques physico-chimiques des couples redox Ce(IV)/Ce(III) et Pu(IV)/Pu(III) tels que le potentiels redox et le coefficient de diffusion dans les milieux N,N-dialkylamides ; des données qui jusque-là, sont quasi-inexistantes dans la littérature. À l’issu de cette étude, une méthode permettant le dosage par voltampérométrie cyclique de cations métalliques en milieu organique a été élaboréeMonoamides extractants are being studied in recent years as alternate extractants to TBP for irradiated nuclear fuels reprocessing. Their extracting strength and selectivity toward Pu(IV) can be tuned depending on the nature of their alkyl chain and the nitric acid concentration. Like TBP, monoamides can extract water and nitric acid while in contact. However, nitric acid is unstable in both aqueous and organic phases. Due to radiolysis, it can be disproportionate in nitrous acid (HNO2) which is known to possess redox properties. It could lead to the formation of the HNO3/HNO2 redox couple which may cause several parasitic redox reactions and affect the recycling process. Meaningful the redox speciation of actinides (An) in an organic phase is important for acute control of the recycling processes. The electrochemical behavior of the Ce(IV)/Ce(III) couple have been studied at 25 and 40°C by cyclic voltammetry at a vitreous carbon working electrode in three N,N-dialkylamides solvents (DEHBA (N,N-di-(2-ethylhexyl)-n-butanamide), DEHiBA (N,N-di-(2-ethylhexyl)-iso-butanamide) and DEHDMBA (N,N-di-(2-ethylhexyl-)3,3-dimethylbutanamide)) pre-equilibrated with aqueous nitric acid solutions (HNO3 5M). Results showed that the Ce(IV)/Ce(III) redox process exhibits a well-defined reversible couple with a diffusion-controlled electrochemical behavior. This initial study on the Ce(IV)/Ce(III) couple, a "non-radioactive model" of the Pu(IV)/Pu(III) couple has been an entry to the direct electrochemical characterization of plutonium in these extractants aiming to identify the nature of the electrochemical process of the Ce(IV)/Ce(III) couple and the difficulties associated with carrying out electrochemical measurements in these viscous and low conductive media. The Pu(IV)/Pu(III) couple has been studied at 40°C in DEHBA at a vitreous carbon working electrode at different concentrations of nitric acid (0,6 M < [HNO3]org < 3,7 M). The study of the speciation of plutonium (IV) in the organic DEHBA phase after extraction showed the presence of two types of plutonium(IV) complexes with variable predominance due to the nitric acid concentration. Cyclic voltammetry measurements showed an significant effect of the speciation of plutonium in the organic phase on the electroactivity of the Pu(IV)/Pu(III) couple. At low nitric acid concentrations, the Pu(IV)/Pu(III) redox process exhibits a well-defined reversible couple with a diffusion-controlled electrochemical behavior. At higher nitric acid concentrations, no electrochemical response of the Pu(IV)/Pu(III) couple is observed. This study enabled the determination of physic and chemical characteristics of the Ce(IV)/Ce(III) and Pu(IV)/Pu(III) couples in N,N-dialkylamides media as the redox potential and the diffusion coefficient that were not previously studied. This study validates the implementation of electrochemical method for the quantification of tetravalent metallic cation in organic phases
3
Berlemont, Romain. "Etude cinétique d'extraction de l'uranium(VI) et du plutonium(IV) par des extractants monoamides." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066320/document.
Повний текст джерелаАнотація:
Ces travaux de thèse, effectués dans le cadre des études sur le retraitement des combustibles nucléaires usés par extraction-liquide-liquide, concernent l’étude cinétique d’extraction de l’uranium(VI) et du plutonium(IV) en milieu acide nitrique par un mélange d’extractants de type monoamide. Trois techniques ont été utilisées pour étudier les cinétiques d’extraction et identifier les régimes de transfert : la méthode de la goutte unique, la cellule d’extraction de Nitsch et la cellule à membrane tournante (RMC). Les résultats obtenus avec la goutte unique indiquent que les cinétiques de transfert d’U(VI) et Pu(IV) sont proches. Une étude hydrodynamique des gouttes et la modélisation du transfert de l’U(VI) ont montré que la présence d’une circulation interne à la goutte diminue les résistances diffusionnelles pour des tailles de goutte croissantes. L’influence de la concentration d’U(VI) dans le solvant sur la cinétique d’extraction a montré que le transfert d’U(VI) et Pu(IV) ralentit lorsque la concentration d’U(VI) en phase organique et la viscosité augmentent. L’ensemble de ces résultats couplé à l’étude du transfert de l’U(VI) par la cellule de Nitsch conduisent à supposer une cinétique gouvernée par la diffusion principalement localisée dans la phase organique. Les études réalisées avec la RMC ont permis de déterminer la constante chimique d’extraction de l’U(VI), du même ordre de grandeur que les cinétiques obtenues par la goutte unique et de confirmer la présence d’une réaction chimique interfaciale. Enfin, le transfert d’U(VI) et Pu(IV) s’avère 3 fois plus lent que celui par le TBP mais reste adapté pour un procédé d’extraction à l’échelle industrielleThis thesis was conducted in the framework of the reprocessing of spent nuclear fuels. The kinetics extraction of uranium(VI) and plutonium(IV) by N,N-dialkylamides or monoamides in an aliphatic diluent were studied from an aqueous nitric solution using 3 different techniques: “single drop technique”, Nitsch cell and Rotating Membrane Cell (RMC). All these experiments were useful to attempt the identification of the transfer process between the phases which can be controlled by kinetic or diffusional regime. The kinetics of extraction of U(VI) by monoamides solvent seems to be similar to that of the Pu(IV). In general, molecular diffusion in organic phase slows down the extraction process and the limiting thickness of organic phase increases with solvent viscosity. The process in “single drop technique” seems to be controlled not only by diffusion but also by the chemical reaction. Then the extraction kinetics of U(VI) has been carried out by Nitsch cell and the RMC. Diffusionnal regime is the limiting step in Nitsch cell and the results confirm that molecular diffusion in organic phase should mainly control the kinetics transfer. Then experiments performed by the RMC indicate that the kinetics is in the same order as transfer coefficient obtained by “single drop” and the chemical reaction occurs at the interface. Finally, these results were compared with data obtained with a TBP solvent (tributyl phosphate) currently used in the PUREX process in order to estimate the interest of such a new solvent. The kinetics of extraction of U(VI) by this monoamide-based solvent is three times lower that of the TBP 30 % but remains fast and suitable for a future industrial process
4
Ribokaite, Kristina. "Etude théorique et expérimentale de complexes d’actinides avec des ligands monoamides et organophosphorés en solution." Paris 6, 2013. http://www.theses.fr/2013PA066458.
Повний текст джерелаАнотація:
Les ligands oxygénés de type monoamides et organophosphorés sont d’un grand intérêt pour le cycle du combustible nucléaire. Ils peuvent permettre d’extraire sélectivement par des procédés d’extraction liquide-liquide certains actinides. La structure de l’extractant, caractérisé par son groupe fonctionnel permettant l’extraction ainsi que par ses substituants alkyles, a un rôle prédominant sur l’extraction sélective des actinides. Ces travaux de thèse concernent l’étude théorique et expérimentale de systèmes modèles afin de mieux comprendre l’effet de la structure de l’extractant sur les structures moléculaires des complexes formés. Ainsi les structures de complexes d’actinides en présence de ligands modèles et dans des milieux simples (eau ou méthanol en présence d’ions nitrate) ont été caractérisées. Des simulations de dynamique moléculaire et des calculs DFT ont permis de quantifier la stabilité des complexes d’uranyle avec des ligands monoamide et oxyde de phosphine et de déterminer leurs propriétés structurales. Les résultats théoriques ont ensuite été confrontés à des résultats expérimentaux obtenus par spectroscopies UV-visible, Infra Rouge, Raman et EXAFS sur des systèmes chimiques identiques. Ensuite, les mesures spectroscopiques associées à la modélisation moléculaire ont permis d’acquérir une meilleure connaissance sur le mode de coordination d’un ion nitrate autour de l’uranyle dans l’eau et le méthanol. Enfin, des calculs DFT ont permis d’étudier l’influence de la structure du ligand monoamide ou organophosphoré sur son interaction avec les actinides (IV, VI) en quantifiant notamment les effets d’encombrement en première sphère de coordinationMonoamides and organophosphate are of great interest for the nuclear fuel cycle. Such ligands can selectively extract actinides in liquid-liquid extraction processes. The structure of the extractant (its functional group and its alkyl substituents) has a predominant role in the selective separation of actinides. This thesis concerns the theoretical and experimental studies of model systems in the aim of better understanding of the effect on molecular structures of the complexes. Structures of actinides complexes formed with model ligands in simple media (water or methanol in the presence of nitrate ions) have been characterized. At first, the complexation of uranyl by monoamide and phosphine oxide was studied in water and methanol. Molecular Dynamics simulations and DFT calculations were used to quantify the stability of uranyl complexes with those ligands, and to determine their structural properties. The theoretical results were then compared with experimental results obtained by UV-visible, infrared, Raman and EXAFS on the same chemical systems. The results were used to highlight the greater stability of uranyl complexes with phosphine oxide and monoamides. Further spectroscopic measurements combined with molecular modeling were used to gain a better understanding of the coordination mode of nitrate ion around the uranyl in both water and methanol. Finally, DFT calculations were used to study the influence of the structure of the monoamide or organophosphorus ligand and their interaction with the actinides (IV, VI) including steric effects in the first coordination sphere
5
Lopes, Moreira Sandra. "Synthèse et évaluation de nouveaux monoamides pour l’extraction de l’uranium(VI) et du plutonium(IV)." Nantes, 2013. https://archive.bu.univ-nantes.fr/pollux/show/show?id=7b1d6f98-ec99-4912-92b1-57de201f818d.
Повний текст джерелаАнотація:
Ces travaux de thèse, effectués dans le cadre des études sur le retraitement des combustibles nucléaires usés par extraction liquide-liquide, concernent la synthèse et l'évaluation de nouveaux monoamides pour étudier l'influence des groupements portés par la fonction amide sur l'extraction de l'uranium(VI) et du plutonium(IV) en milieu acide nitrique. Dans ce contexte, quarante-deux nouveaux monoamides, comportant des modifications soit du côté carbonyle soit du côté de l'atome d'azote, ont été synthétisés. Ces monoamides ont été conçus dans l'intention d'établir une relation entre la structure des monoamides et leur affinité et sélectivité vis-à-vis de l'U(VI) et Pu(IV). Des tests d'extraction ont été réalisés à 4M et 0,5M HN03 afin d'estimer les coefficients de distribution et la sélectivité U(VI)/Pu(IV). Les résultats ont confirmé l'influence des ramifications en a ou ß du carbonyle pour la sélectivité U/Pu, et ont également montré l'importance de la ramification des chaines azotées. Le comportement singulier des monoamides comportant des chaines dissymétriques sur l'atome d'azote vis-à-vis de l'extraction du Pu(IV) a permis de concevoir une molécule plus performante que la molécule de référence. Enfin, des études complémentaires sur deux ligands pertinents ont été menées pour déterminer la stœchiométrie des complexes actinides-ligand formés en phase organique, et pour évaluer le potentiel d'une molécule dans des conditions proches de celles du procédéThis thesis, conducted in the framework of the reprocessing of spent nuclear fuels, concerns the design and evaluation of new monoamides to study the influence of the branched alkyl groups grafted on the amide function on uranium (VI) and plutonium (IV) extraction. Forty two new monoamides, with modifications on carbonyl side or on the nitrogen atom side, were synthesized. These monoamides were designed in order to establish a relationship between the monoamide structure and its affinity and selectivity relatively towards U(VI) and Pu(IV). Liquid-liquid extraction tests were systematically performed with these ligands at 4M and 0,5M HN03 in order to measure the distribution ratios and the U(VI)/Pu(IV) selectivity. The results confirmed the strong influence of the steric hindrance due to branched alkyl groups on the carbonyl side on the U(VI)/Pu(IV) selectivity but have also shown the importance of the steric hindrance on the nitrogen side. The single behaviour of the unsymmetrical monoamides observed for Pu(IV) extraction allowed the design a new molecule with higher performances than the reference monoamide. Finally, extractions isotherms on two relevant ligands were performed in order to determine the stoichiometry of the actinide-ligands complexes formed in organic phase and to assess the performances of this new ligand in process conditions
6
Moeyaert, Pauline. "Etude expérimentale et modélisation des mécanismes d’extraction des produits de fission et des actinides mineurs par des extractants de la classe des monoamides." Thesis, Montpellier, 2016. http://www.theses.fr/2016MONTT199.
Повний текст джерелаАнотація:
Le procédé PUREX utilise comme molécule extractante le tri-butyl-phosphate (TBP) pour assurer l’extraction et la purification de l’uranium et du plutonium des combustibles nucléaires usés. Bien que le retour d’expérience industriel soit très positif, des améliorations de ce procédé sont possibles notamment pour le futur traitement de combustibles plus riches en plutonium. Les extractants de la famille des N,N-dialkylamides (monoamides) ont montré par le passé une potentialité avérée pour remplacer le TBP : ils permettent de co-extraire l’uranium et le plutonium puis de dés-extraire sélectivement le plutonium par une diminution de l’acidité du milieu, supprimant ainsi les opérations de réduction du plutonium consommatrices en réactif potentiellement toxique (hydrazine). Le travail de recherche mené au cours de cette thèse vise à comprendre et modéliser l’extraction de certains produits de fission et actinides mineurs : césium, europium, américium, ruthénium et technétium, éléments qui ne doivent pas contaminer les matières recyclées. Les systèmes extractants choisis pour l’étude sont constitués des monoamides N,N-di (éthyl-2 hexyl) butanamide (DEHBA), N,N-di (éthyl-2 hexyl) isobutanamide (DEHiBA), du mélange de ces deux monoamides, de N-méthyl-N-octyl-(2-ethyl)hexanamide (MOEHA) et de TBP, extractant actuellement utilisé à l’usine AREVA de La Hague, dilués dans le tétrapropylène hydrogéné (TPH). Pour y parvenir, une démarche multi-échelle a été mise en place avec l’acquisition de données de distribution et de données thermodynamiques. Ces données ont servi de support pour élaborer des modèles permettant de simuler le comportement des différents éléments dans les cycles d’extraction actuel ou futur. En parallèle et lorsque les conditions chimiques des systèmes le permettaient, des études de spéciation des phases organiques ont été entreprises, afin d’obtenir des informations sur la stœchiométrie des complexes formés et sur les mécanismes mis en jeu au cours de l’extraction.De ces travaux peuvent se dégager un certain nombre de conclusions :- l’extraction des nitrates de césium, d’europium et d’américium par les monoamides est très faible et a pu être correctement modélisée,- l’extraction du technétium par les monoamides semble répondre au même mécanisme que dans le cas du TBP : le technétium est principalement co-extrait en phase organique en formant des complexes mixtes avec l’uranium. En effet, un anion pertechnétate se substitue à un anion nitrate dans les complexes formés entre l’extractant et le nitrate d’uranyle, selon un mode de coordination monodenté, conduisant à une extraction exacerbée du technétium. La modélisation de l’extraction du technétium par les monoamides a pu être améliorée en reconsidérant l’estimation des écarts à l’idéalité en phase aqueuse avec une nouvelle variation du coefficient d’activité de l’acide pertechnétique en solution binaire dans l’eau,- avec les monoamides comme avec le TBP, le ruthénium est faiblement extrait en phase organique mais cette fraction extraite, aussi faible soit elle, constitue une contamination résiduelle du solvant. Les données acquises, grâce à la mise au point d’un protocole de préparation de solutions simulées, sont représentatives du comportement du ruthénium dans les conditions d’extraction des procédés. Les modèles développés permettent de très bien reproduire le comportement du ruthénium dans les opérations d’extraction de procédés mis en œuvre à l’échelle pilote, sur des solutions de dissolution réelles,- une approche nouvelle pour le calcul des coefficients d’activité en phase organique a été développée. Elle explicite les écarts à l’idéalité liés à l’association en phase organique via les équilibres de complexation, mais aussi, et pour la première fois, les effets liés à la répulsion entre espèces en les considérant comme des sphères duresThe PUREX process is a solvent extraction method dedicated to the reprocessing of irradiated nuclear fuel in order to selectively extract uranium(VI) and plutonium(IV) from fission products and minor actinides. The tri-n-butylphosphate (TBP) is used as the extractant in the organic phase. Within the frame of the development of Generation IV reactors, new liquid-liquid extraction processes are under development for the reprocessing of spent nuclear fuels. The N,N-dialkylamides (monoamides) already showed their potentiality as promising alternative extractant to TBP for nuclear fuel reprocessing: they are able to extract U(VI) and Pu(IV) selectively by adjusting the nitric acid concentration without using Pu(IV) reducing agents. This study aims at understanding and modeling the extraction of some fission products and minor actinides: cesium, europium, americium, ruthenium and technetium, which may occur as impurities in the organic phase. In the present study, the extraction properties of N,N-di (ethyl-2 hexyl) butanamide (DEHBA), N,N-di (ethyl-2 hexyl) isobutanamide (DEHiBA), as well as a mixture of these two monoamides, N-methyl-N-octyl-(2-ethyl)hexanamide (MOEHA) and TBP, the extractant currently used in the PUREX process at the La Hague plant, diluted in TPH, were studied. For that purpose, a multi-scale approach has been used to describe the extraction mechanisms combining two different descriptions. Distribution and thermodynamic data were first determined from batch experiments. Based on these data, thermodynamic models were developed and are able to predict the behaviour of the different elements in current or future processes. Dedicated methods were also performed to obtain information about the stoichiometry of the extracted species and about the mechanisms involved during the extraction step.The main conclusions that can be deduced from this study are:- even if the extraction of cesium, europium and americium nitrates with monoamides is very low, models have been developed and fit the experimental data with good agreement,- the same mechanism may be involved in the extraction of technetium with TBP or monoamides: technetium is preferentially co-extracted in organic phase as mixed uranium-technetium species. Indeed, one TcO4- anion replaces one NO3- ion in a monodentate coordination mode in the uranium-monoamide complex. The developed thermodynamic models, that have been improved by taking into account a new variation of the pertechnetic acid activity coefficient in binary solution, fit very well the experimental data,- with monoamides as with TBP, ruthenium is poorly extracted but remains troublesome in the spent fuel reprocessing industry because of its retention in the irradiated solvent. Distribution data have first been determined from batch experiments thanks to the development of a new methodology for simulated ruthenium spent fuel dissolution solutions preparation. The developed thermodynamic models fit very well the batch experimental data. Thus, they was then used to simulate ruthenium behaviour in counter-current hot tests performed in mixer-settlers- a new approach for the activity coefficient calculation in organic phase has been developed. The MSA theory (Mean Spherical Approximation) was chosen for this purpose to explicitly describe both association and repulsive forces.Finally, this work that includes a macroscopic study (distribution and thermodynamic data acquisition and modeling) and molecular investigations (ESI-MS, FT-IR and X-ray absorption analysis supported by theoretical calculations) provides a new insight in the description of solvent extraction mechanism
7
Rabbe, Catherine. "Apport de la modélisation moléculaire et des relations structure-activité à l'extraction liquide-liquide. Application au cas de l'extraction d'U(VI) par les monoamides." Rouen, 1996. http://www.theses.fr/1996ROUES028.
Повний текст джерелаАнотація:
La modélisation moléculaire a été utilisée dans le domaine de l'extraction liquide-liquide de l'uranium (VI) par les monoamides à partir d'un milieu nitrique. Trois types de paramètres importants à étudier ont été identifiés : la réactivité des atomes du site de coordination, l'encombrement stérique et la lipophilie des ligands. L'objectif est, par les méthodes de la modélisation moléculaire, de calculer les paramètres mentionnés plus haut et d'établir des relations entre la structure moléculaire de l'extractant ou de son complexe formé avec le cation métallique et ses propriétés extractantes. Une base expérimentale de 22 N, N-dialkylamides a été sélectionnée. Tout d'abord, les méthodes semi-empiriques de la chimie quantique ont été utilisées afin de calculer les structures des monoamides et les propriétés physico-chimiques correspondantes. La somme des charges des atomes au voisinage du site réactif a pu être reliée au coefficient de distribution de l'uranium. Puis les outils de la mécanique moléculaire ont été utilisés pour calculer la structure des complexes UO2(NO3)2(amide)2 formés. Après une étape préliminaire de paramétrisation du champ de force pour traiter U(VI), le calcul de 22 structures de complexes nitrate d'uranyle - monoamides a été réalisé. Une relation a été montrée entre le coefficient de distribution d'U(VI) et la composante stérique de l'énergie d'association du complexe (i. E. La différence entre l'énergie du complexe et celle des espèces prises séparément). Enfin, un modèle prédictif de la capacité à extraire U(VI) a été établi pour 19 molécules de la base de données expérimentales (N,N-diakylamides). Ce modèle permet de prévoir le coefficient de distribution d'U(VI) à partir des paramètres électronique (calculé en chimie quantique) et stérique (calculé en mécanique moléculaire). Il a été montré que, dans ce cas, la lipophilie des ligands n'est pas un facteur déterminant.
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Rabbe, Catherine. "Apport de la modélisation moléculaire et des relations structure-activité à l'extraction liquide-liquide : application au cas de l'extraction d'U(VI) par les monoamides /." Gif-sur-Yvette : Direction de l'information scientifique et technique, CEA Saclay, 1996. http://catalogue.bnf.fr/ark:/12148/cb369615416.
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CitÃ, Maria do Carmo de Oliveira. "AlteraÃÃes comportamentais e neuroquÃmicas provocadas por diferentes perÃodos de retirada apÃs tratamento subcrÃnico com cocaÃna em ratos: envolvimento dos sistemas dopaminÃrgico, serotonÃrgico e noradrenÃrgico." Universidade Federal do CearÃ, 2009. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=3986.
Повний текст джерелаАнотація:
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorA cocaÃna à uma droga consumida mundialmente e considerada hoje como um problema de saÃde pÃblica. Uma das principais dificuldades enfrentadas no combate ao vÃcio da cocaÃna, na maioria dos casos, està relacionada aos sintomas de abstinÃncia da droga, como ansiedade, depressÃo, irritabilidade, fadiga e insÃnia, fazendo com que o indivÃduo volte a procurÃ-la. Para avaliar as alteraÃÃes comportamentais (ansiedade e depressÃo) e neuroquÃmicas, os ratos foram submetidos Ãs retiradas de 24 h, 7 d e 21 d apÃs o tratamento subcrÃnico por 7 dias com cocaÃna (20mg/kg), sendo realizados os modelos experimentais de Labirinto de Cruz Elevado (LCE), Campo Aberto (CA) e Nado ForÃado (NF). AlÃm disso, na abstinÃncia de 24h foram testados o propranolol (10mg/kg, i.p.), o ondansetrom (4mg/kg, i.p) e a buspirona (5 mg/kg, i.p.), no LCE e CA, bem como na abstinÃncia de 21 d foram testados a bupropiona (30mg/kg, i.p.) e paroxetina (10 mg/kg, i.p.) no NF, com o intuito de reverter tais alteraÃÃes comportamentais provocadas pela retirada forÃada do tratamento subcrÃnico com cocaÃna. Para o estudo neuroquÃmico (neuroadaptaÃÃo) foi utlizado o corpo estriado (CE) de ratos, avaliando-se os seguintes parÃmetros: nÃveis de monoaminas (NA, DA, 5-HT) e seus metabÃlitos (DOPAC, HVA e 5-HIAA) atravÃs do HPLC com detecÃÃo eletroquÃmica e a atividade da enzima catalase. Na avaliaÃÃo da ansiedade, os resultados mostraram que no LCE houve uma reduÃÃo do NEBA, PEBA, TPBA e PTBA na abstinÃncia de 24h e 7 d, apÃs 21d nÃo houve alteraÃÃo. No CA, as retiradas de 24h e 7 d promoveram um aumento da atividade locomotora do animal, no entanto na retirada de 21 d ocorreu uma diminuiÃÃo da atividade locomotora. Na abstinÃncia de 24h foram administrados propranolol, ondansetrom e buspirona. No LCE, o propranolol aumentou o NEBA e reduziu o PTBA, enquanto que o ondansetrom aumentou o NEBA, PEBA, TPBA e o PTBA em relaÃÃo ao grupo da cocaÃna. Jà a buspirona em relaÃÃo à cocaÃna aumentou o PTBA, TPBA e o PEBA, porÃm o NEBA foi reduzido. Enquanto que no CA, o propranolol, o ondansetrom e a buspirona reduziram a atividade locomotora em relaÃÃo ao grupo da cocaÃna. Para avaliar a atividade antidepressiva foi realizado o teste do nado forÃado, no qual as retiradas de 24h e 7 d reduziram o tempo de imobilidade, contudo na abstinÃncia de 21 d houve um aumento do parÃmetro avaliado. Na abstinÃncia de 21 d foram administrados paroxetina e bupropiona, verificando uma reduÃÃo do tempo de imobilidade em relaÃÃo ao grupo da cocaÃna. Para a realizaÃÃo dos estudos neuroquÃmicos, os animais foram dissecados para retirada do CE. No corpo estriado observou-se um aumento de dopamina (DA) e uma reduÃÃo de seus metabÃlitos (DOPAC e HVA) nas trÃs retiradas. A concentraÃÃo de serotonina aumentou nas trÃs retiradas, entretanto o seu metabÃlito (5HIAA) aumentou somente nas retiradas de 24h e 7d. Jà a noradrenalina reduziu apÃs as trÃs retiradas. Em relaÃÃo aos receptores, no corpo estriado D2 encontrava-se elevado em 24h e 7d, jà 5HT2 apÃs 7d e D1 nÃo foi alterado. Foi tambÃm avaliado no CE a atividade da catalase, enzima antioxidante, que mostrou uma reduÃÃo de sua atividade nas trÃs retiradas. Os resultados sugerem que diferentes perÃodos de retirada apÃs tratamento subcrÃnico com cocaÃna causam efeitos ansiogÃnicos e depressores sobre o SNC e tais efeitos foram revertidos por propranolol, ondansetrom, buspirona, bupropiona e paroxetina. O estudo neuroquÃmico mostrou que a abstinÃncia de cocaÃna sÃo eventos multimediados e que CE tem uma importante participaÃÃo, estando tambÃm a atividade da catalase envolvida neste processo. Estes achados sÃo importantes para a investigaÃÃo de novos tratamentos para a sÃndrome de abstinÃncia de cocaÃna.
Cocaine is world used and considered as a public health problem, being the relapse one of the hardly difficulties faced by cocaine users, that in the most cases, is related to abstinence symptoms, like anxiety, depression, irritability, fatigue and sleeplessness. To evaluate the behavioral alterations (anxiety and depression) and neurochemistry, rats were submitted to 24h, 7 d and 21 d withdrawal, after the subcronic treatment, for 7 days with cocaine (20mg/kg), being realized the experimental models of Elevated Plus Maze (EPM), Open Field (OF) and Forced Swimming (FS). Moreover, in the 24h abstinence, propranolol (10mg/kg, i.p.), ondansetrom (4mg/kg, i.p) and buspirone (5 mg/kg, i.p.) had been tested, in the EPM and OF, as wel as in the 21 d of abstinence bupropione (30mg/kg, i.p.) and paroxetine (10 mg/kg, i.p.) had been tested in the FS, aiming to revert the alterations caused by the abstinence of cocaine subcronic administration. For the neurochemistry study (neuroadaptation) was used striatum (ST) of rats, evaluating the following parameters: level of monoamines (NE, DA and 5HT) and its metabolites (DOPAC, HVA and 5HIAA), using the electrochemistry detection HPLC and the activity of the catalase enzyme. In the anxiety evaluation, results showed that in the EPM there was a reduction on NEOA, PEOA, TPOA and PTOA in the abstinence of 24h, 7 d and 21 d. In the OF, the withdrawal of 24 and 7 d promoted an increasing in the locomotor activity of animals, while the withdrawal of 21 d a decreasing in the locomotor activity was observed. In the 24h abstinence were administered propranolol, ondansetrom and buspirone. In the EPM, propranolol increased NEOA and reduced PTOA, while ondansetrom increased NEOA, PEOA, TPOA and PTOA, as compared to cocaine group. In addition buspirone as compared to cocaine group increased PTOA, TPOA, and PEOA, however NEOA was reduced. While in the OF, propranolol, ondansetron and buspirone reduced the locomotor activity as related to cocaine group. To evaluate the antidepressive effect the FS was performed, where the withdrawal of 24h and 7 d reduced the immobility time, although in the 21 d abstinence an increase of this parameter was observed. In the 21 d abstinence had been administered paroxetine and buproprione, verifying a reduction of the immobility time as related to cocaine group. To the performance of neurochemistry studies, animals were dissected to take off the ST. In the ST was observed an increasing of dopamine (DA) and a reduction of its metabolites (DOPAC and HVA) in the three withdrawals. The serotonine levels increased the three withdrawals, however its metabolite (5HIAA) increased only in the 24h and 7 d withdrawals. In addition norepinephrine reduced after the 24h, 7 d and 21 d withdrawal. In relation to the receptors, in the ST D2 24h and 7d met high in, already 5HT2 after 7d and D1 was not alteration. Were evaluated too in the ST the activity of catalase, antioxidant enzyme, that showed a reduction of your activity in the three withdrawal. Results suggests that different times of withdrawal after subcronic treatment with cocaine cause anxyogenic and depressive effects on the CNS and this effects were reverted by the administration of drugs (propranolol, ondansetrom, buspirone, bupropione and paroxetine). The neurochemistry study showed that the abstinence of cocaine were events multimediated and the brain area study ST has an important role, being the catalase activity involved in this process. These findings are important to the investigation of new treatments to the cocaine abstinence syndrome.
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Aguiar, Lissiana Magna Vasconcelos. "Efeitos comportamentais e neuroquÃmicos da melatonina em ratos submetidos à lesÃo estriatal com 6-ohda." Universidade Federal do CearÃ, 2002. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=19.
Повний текст джерелаАнотація:
Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgicoOs efeitos da melatonina (Mel) in vivo foram estudados no sistema dopaminÃrgico nigroestriatal de ratos, utilizando um modelo experimental da doenÃa de Parkinson que consiste na injeÃÃo intraestriatal da neurotoxina 6-hidroxidopamina (6-OHDA). Ratos Wistar, machos (200-250g) foram submetidos a lesÃo unilateral com 6-OHDA, tratados com melatonina nas doses de 2, 5, 10 e 25 mg/kg, i.p. 1 hora apÃs a lesÃo e depois, diariamente durante 7 dias, quatro semanas apÃs a lesÃo, foi realizado o teste rotacional e 24 horas depois os animais foram sacrificados, os seus cÃrebros dissecados e os estriados direito (ipsilateral â lado lesionado) e esquerdo (contralateral â lado nÃo lesionado) utilizados para dosagens de monoaminas em HPLC e ensaios de binding dopaminÃrgico. Para as dosagens de malonildialdeÃdo (MDA), os animais foram sacrificados no oitavo dia apÃs a lesÃo. Os resultados demonstraram que a injeÃÃo intraestriatal de 6-OHDA diminuiu cerca de 77 à 85% os conteÃdos das monoaminas e dos seus metabÃlitos no lado ipsilateral quando comparado com o lado contralateral nos controles. O tratamento com melatonina, nas doses estudadas, reverteu parcialmente as diminuiÃÃes causadas pela lesÃo com 6-OHDA nos nÃveis destes neurotransmissores, e os conteÃdos se aproximaram de 50% daqueles observados nos lados contralaterais dos controles ou dos grupos tratados com melatonina. A Mel foi mais eficiente na dose de 5 mg/kg, i.p., e os efeitos foram similares entre as doses mais baixas e as mais altas, caracterÃstica de um tipo de resposta com a curva em forma de sino. O prÃ-tratamento e o tratamento crÃnico com melatonina na dose que obteve o melhor efeito tambÃm foram estudados, o tratamento crÃnico promoveu uma melhor recuperaÃÃo dos nÃveis de monoaminas enquanto os efeitos do prÃ-tratamento foram similares aos do grupo Mel 5 mg/kg, durante 7dias. O comportamento rotacional induzido pela apomorfina (3 mg/kg) foi bloqueado em cerca de 60, 89, 78 e 47% nos grupos tratados com melatonina nas doses de 2, 5, 10 e 25 mg/kg, i.p., respectivamente. O tratamento crÃnico bloqueou o comportamento rotacional em cerca de 96% e o prÃ-tratamento 86%. A melatonina (5 mg/kg) produziu uma upregulation dos receptores D1 (Bmax: 277,8+/-25,8) associada com uma diminuiÃÃo nos valores do Kd (1,5+/-0,1) quando comparado ao controle (Bmax:194,8+/-19,0; Kd:2,9+/-0,38). Um efeito similar foi observado com o tratamento com NAS (Bmax: 245,3+/-27,6; Kd: 1,1+/-0,28), precursor da melatonina. Foi verificado um aumento nos nÃveis de MDA, nos controles (127%), quando comparado com o grupo falso operado (104%), o tratamento com melatonina (106%) recuperou esses nÃveis à valores prÃximos do normal, sugerindo uma aÃÃo antioxidante da melatonina in vivo. Os resultados apresentados podem indicar uma aÃÃo neuroprotetora da melatonina e sugerem um possÃvel papel no tratamento de doenÃas neurodegenerativas causadas pelo estresse oxidativo, como a doenÃa de Parkinson.
The present work studied the neuroprotective effects of melatonin In vivo on the nigrostriatal dopaminergic system in rats after a unilateral 6-hydroxydopamine (6-OHDA) lesions in rat striatum. Results showed that the intrastriatal injection of 6-OHDA significantly decreases DA, DOPAC and HVA levels. Although there is also a decrease in 5-HT levels no changes were observed in 5-HIAA levels as compared to controls. On the other hand, melatonin (2, 5, 10 and 25 mg/kg, i.p., daily for 7 days) treatment starting 1 h after 6-OHDA lesions, partially reverses the decreases caused by 6-OHDA lesions on these neurotransmitter levels, and contents were brought to approximately 50% of that observed in the contralateral sides of controls or the melatonin treated group. Melatonin was more efficient at the doses of 5 and 10 mg/kg, i.p., and effects were similar between the lowest and highest doses characteristic of a bell-shaped type of response. Pretreatment and cronic treatment with melatonin at the 5mg/kg dose were also tested, cronic treatment promoted a recovey of monoamines levels more efficiently while the pretreatment effects were similar to the melatonin treatment at the dose of the 5mg/kg for 7 days. The apomorphine-induced rotational behavior (3 mg/kg, i.p.) was blocked by 60, 89, 78 and 47% after the doses of 2, 5, 10 and 25 mg/kg, i.p., respectively. Similarly, in this case the doses of 5 and 10 mg/kg were also more efficient. The cronic treatment blocked the rotational behavior by 86%. Melatonin (5mg/kg) produced an upregulation of D1 receptors associated with a decrease in Kd value. While no change was observed in maximum density of D2 receptors, the Kd value was also decreased, a similar effect was observed with its precursor N-acetylserotonin. Compared with sham-operated and expressed as a ratio relative to the contralateral side, there was an increase in the lipid peroxidation product malondialdehyde (MDA, 127%) on controls which was restored to normal levels on the melatonin treated group, suggesting the in vivo action of melatonin as an antioxidant. The present results may indicate a neuroprotective action of melatonin and suggest a possible role in the treatment of oxidative stress-induced neurodegenerative disease such as Parkinsonâs disease.
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Kaushal, Setu. "Characterization of Three Putative Monoamine Oxidase Genes in Caenorhabditis elegans." Ohio University / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1218747926.
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Patil, Dadasaheb V. "Intramolecular cyclization strategies for synthesizing medium-ring polycycles and the total synthesis of natural products." Diss., Georgia Institute of Technology, 2012. http://hdl.handle.net/1853/50118.
Повний текст джерелаАнотація:
Carbo- and heterocyclic compounds are of great interest to chemists. Intramolecular cyclization strategies of donor-acceptor (D-A) cyclopropanes and alkylidene malonate monoamides have excellent potential for synthesis as they offer easy access to structurally-diverse compounds. The work described in this thesis accesses the scope of the In(OTf)3-catalyzed cyclization reaction of cyclopropanes and alkylidene malonate monoamides. In(OTf)3-catalyzed reactions of alkenyl and heteroaryl cyclopropyl ketones were examined in the synthesis of functionalized cyclohexenone-based derivatives (Chapter 2). Subsequent efforts to utilize a tandem cyclopropane ring-opening/Friedel-Crafts alkylation sequence of methyl 1-(1H-indolecarbonyl)-1-cyclopropanecarboxylates to prepare functionalized hydropyrido[1,2-a]indole-6(7H)-ones is discussed in Chapter 3. The extension of this tandem protocol towards the total synthesis of (±)-deethyleburnamonine is the subject of Chapter 6. Intramolecular Friedel-Crafts alkylation of N-indolyl alkylidene malonate monoamides was also examined. An In(OTf)3-catalyzed cyclization of substituted methyl 2-(1H-indole-1-carbonyl) acrylates afforded a series of 1H-pyrrolo[1,2-a]indole-3(2H)-ones (Chapter 4), whereas substrates with the indole 2-position blocked provided access to substituted 4H-pyrrolo[3,2,1-ij]quinolin-4-ones (Chapter 5).
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VenÃncio, Edith Teles. "Estudo dos efeitos comportamentais e neuroquÃmicos do extrato padronizado de Justicia pectoralis (chambÃ) em camundongos." Universidade Federal do CearÃ, 2009. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=3935.
Повний текст джерелаАнотація:
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorO extrato padronizado de chambÃ, preparado a partir das partes aÃreas da Justicia pectoralis Jacq. var stenophylla Leonard, foi avaliado em modelos animais clÃssicos para screening de drogas com atividade em ansiedade, depressÃo, sedaÃÃo e convulsÃo, tais como, labirinto em cruz elevado (LCE), claro/escuro, campo aberto, rota rod, nado forÃado, suspensÃo da cauda, tempo de sono induzido por pentobarbital e convulsÃo induzida por pentilenotetrazol, e em estudo neuroquÃmico, atravÃs da concentraÃÃo de monoaminas e seus metabÃlitos, tais como dopamina (DA), Ãcido diidrofenil acÃtico (DOPAC), Ãcido homovalÃnico (HVA), noradrenalina (NE), 5-hidroxitriptamina (5-HT) e Ãcido 5-hidroxindolacÃtico (5-HIAA). O chambà foi administrado de forma aguda em todos os testes, nas doses de 50, 100 e 200 mg/kg, atravÃs da via oral (v.o.) Os resultados mostraram que o extrato apresentou efeito ansiolÃtico nos modelos LCE e claro/escuro, pois aumentou todos os parÃmetros analisados no LCE, como NEBA, PEBA, TPBA e PTBA, assim como o tempo de permanÃncia no box claro no claro/escuro. Este efeito està possivelmente relacionado com o sistema gabaÃrgico jà que o flumazenil, antagonista dos receptores GABAA/BenzodiazepÃnico, reverteu o efeito ansiolÃtico do chambà no LCE. No teste do campo aberto, nÃo foi observado nenhuma alteraÃÃo na atividade locomotora, bem como no nÃmero de grooming e rearing. O chambà apresentou efeito depressor do Sistema Nervoso Central (SNC), pois nos testes nado forÃado e suspensÃo da cauda, aumentou o tempo de imobilidade dos animais. A avaliaÃÃo sedativa/hipnÃtica do chambÃ, no teste do tempo de sono induzido por pentobarbital, mostrou que nÃo houve alteraÃÃo na duraÃÃo do sono dos animais, descartando efeito sedativo. No teste da convulsÃo induzida por pentilenotetrazol, o chambà nÃo alterou a latÃncia de convulsÃo, bem como a latÃncia de morte. Esse resultado sugeriu que o chambà nÃo possui efeito anticonvulsivante. A avaliaÃÃo neuroquÃmica comprovou o efeito depressor do extrato, pois foi verificada uma reduÃÃo da concentraÃÃo das monoaminas. Em conclusÃo, esses efeitos mostraram que o chambà apresenta efeito ansiolÃtico, provavelmente relacionado com o sistema gabaÃrgico e efeito depressor, desprovido de atividade anticonvulsivante e sedativa.
The standardized extract of chamba, prepared from the aerial parts of Justicia pectoralis Jacq. var stenophylla Leonard, was evaluated in classical animal models to the screening of drugs with activity in axiety, depression, sedation and convulsion, such as elevated plus maze (EPM), light/dark, open field, rota rod, forced swimming, tail suspension, pentobarbital-induced sleep time and pentilenotetrazole-induced seizures and a neurochemistry study, through the level of monoamines and its metabolites, such as dopamine (DA), 3,4-dihydroxyphenyl acetic acid (DOPAC), homovanilic acid (HVA), norepinephrine (NE), 5-hydroxytryptamine (5HT) and 5-hydroxyindoleacetic acis (5HIAA). Chambà was administered acutely in all tests, in the doses of 50, 100 and 200 mg/kg, through the oral via (p.o.). Results showed that the extract presented an anxiolytic effect in the models of EPM and light/dark, since increased all the parameters analyzed in the EPM, such as NEOA, PEOA, TPOA, PTOA, as well as the permanence time in the light compartment. This effect is probably related with the GABAergic system since Flumazenil, an antagonist of GABAA/benzodiazepinic, reversed the anxiolytic effect of chamba in the EPM. In the open field, it was not observed any alteration in the locomotor activity, as well as the number of grooming and rearing. Chamba presented depressor effect of Central Nervous System (CNS), since in the forced swimming and tail suspension, increased the immobility time of animals. The sedative/hypnotic evaluation of chamba, in pentobarbital-induced sleep time showed that it has no alteration in the duration of sleep of animals, discarding sedative effect. In the pentilenotetrazole-induced seizures, chamba did not change the convulsion latency, as well the death latency. This result suggests that chamba did not have anticonvulsivant effect. The neurochemistry evaluation comproved the depressor effect of the extract, since it was verified a reduction in the level of monoamine levels, involved in the depression. In conclusion, these effects showed that chamba presented anxiolytic effect, probably related with the GABAergic system and depressor effect disproved anticonvulsant and sedative effects.
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Moura, Brinell Arcanjo. "AlteraÃÃes comportamentais, neuroquÃmicas e glicolipÃdicas em ratos tratados com Hoodia gordonii, um supressor natural do apetite." Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=8886.
Повний текст джерелаАнотація:
Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgicoHoodia gordonii à uma planta da famÃlia das apocinÃceas. OriginÃria do sudeste da Ãfrica, onde tem sido historicamente usada para suprimir o apetite durante longas jornadas de caÃa, sendo utilizada em diversos paÃses com o objetivo de emagrecer. No Brasil foi retirada do mercado devido à falta de estudos que comprovem sua eficÃcia e seguranÃa para o uso. O objetivo deste trabalho foi avaliar as alteraÃÃes comportamentais, neuroquÃmicas e glicolipÃdicas em ratos tratados com Hoodia gordonii. Para a realizaÃÃo deste estudo H. gordonii foi administrada por via oral nas doses de 25 e 50 mg/Kg durante oito dias consecutivos em ratos Wistar machos (160-200g), D-anfetamina 2 mg/Kg foi administrada intraperitonealmente de forma aguda e usada como padrÃo positivo. Os testes aconteceram 60 minutos apÃs o ultimo dia de tratamento com a Hoodia e 30 minutos apÃs o tratamento com D-anfetamina. Foram avaliados a variaÃÃo de peso dos animais durante o tratamento, bem como o consumo de Ãgua e comida. Para os testes comportamentais foram feitos os testes de labirinto em cruz elevado, campo aberto e placa perfurada. Para os estudos neuroquÃmicos foi feito HPLC com detecÃÃo eletroquÃmica. Para os testes glicolipÃdicos foi feita dosagem de Glicose, HDL, LDL, TG, colesterol total, ALT e AST. Os resultados mostraram que H. gordonii à capaz de reduzir o ganho de massa corpÃrea, bem como reduzir o consumo de comida e Ãgua. Os resultados dos testes comportamentais mostraram que ela à capaz de reduzir os parÃmetros observados no teste do labirinto em cruz e placa perfurada sem mostrar alteraÃÃo significante no campo aberto. Os resultados dos experimentos neuroquÃmicos evidenciaram um aumento do conteÃdo de noradrenalina e dopamina em corpo estriado de ratos, detectados eletroquimicamente pelo HPLC. Nos testes bioquÃmicos foi visto que ela tem a capacidade de reduzir os nÃveis de glicose, bem como a concentraÃÃo de triglicerÃdeos e colesterol total em soro de ratos, sem mostrar alteraÃÃo significante da ALT e AST. Foi possÃvel concluir que H. gordonii à capaz de reduzir a ingestÃo de alimentos e que este efeito pode estar de alguma forma ligado à neurotransmissÃo noradrenÃrgica e dopaminÃrgica, possuindo tambÃm atividade ansiogÃnica evidenciada pelos estudos comportamentais.
Hoodia gordonii is a plant of the family apocinaceae. Originally from southeastern Africa, where it has historically been used to suppress appetite during long hunting trips, being used in several countries in order to lose weight. In Brazil was withdrawn from the market due to lack of studies proving its efficacy and safety for use. The aim of this study was to evaluate the behavioral changes and neurochemical glicolipÃdicas in rats treated with Hoodia gordonii. For this study H. gordonii was administered orally at doses of 25 and 50 mg/kg for eight consecutive days in male Wistar rats (160-200g), D-amphetamine 2 mg/kg was intraperitoneally administered acutely and used as a positive standard. The tests took place 60 minutes after the last day of treatment with the Hoodia and 30 minutes after treatment with D-amphetamine. We evaluated the weight change of the animals during treatment, as well as the consumption of water and food. For behavioral tests were performed tests elevated plus-maze, open field and hole board. For neurochemical studies was done HPLC with electrochemical detection. For testing was done glycolipid glucose, HDL, LDL and TG, total cholesterol, ALT and AST. The results showed that H. gordonii is capable of reducing body mass gain and reduce the consumption of food and water. The results of behavioral tests showed that it is able to reduce the parameters observed in the plus-maze test and hole board showing no significant change in the open field. The results of experiments showed an increase in the neurochemical content of noradrenaline and dopamine in the striatum of rats electrochemically detected by HPLC. In biochemical tests it was seen that it has the ability to lower blood glucose levels as well as the concentration of triglycerides and total cholesterol in serum from mice, showing no significant change in ALT and AST. It was concluded that H. gordonii is able to reduce food intake, and this effect may be somehow linked to the dopaminergic and noradrenergic neurotransmission, having also anxiogenic activity evidenced by behavioral studies.
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Linhares, Maria Isabel. "Estudo da Ritalina (Cloridrato de Metilfenidato) sobre o sistema nervoso central de animais jovens e adultos: aspectos comportamentais e neuroquÃmicos." Universidade Federal do CearÃ, 2012. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=9347.
Повний текст джерелаАнотація:
CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel SuperiorO Transtorno de DÃficit de AtenÃÃo/ Hiperatividade (TDAH) Ã um transtorno prevalente e debilitante, diagnosticado com base em persistentes nÃveis de hiperatividade, desatenÃÃo e impulsividade. FÃrmacos estimulantes tÃm sido eficazes no tratamento desse transtorno, sendo que o metilfenidato (MFD) Ã o agente terapÃutico mais prescrito e seu uso aumentou significativamente nos Ãltimos anos, entretanto, as conseqÃÃncias da sua utilizaÃÃo ainda sÃo pouco conhecidas. O MFD foi avaliado em modelos animais clÃssicos para screening de drogas com atividade em ansiedade, depressÃo e convulsÃo, tais como, labirinto em cruz elevado (LCE), campo aberto, rota rod, nado forÃado e convulsÃo induzida por pilocarpina, e em estudo neuroquÃmico, atravÃs da concentraÃÃo de monoaminas, tais como dopamina (DA), noradrenalina (NE) e 5-hidroxitriptamina (5-HT), alÃm da atividade da enzima Acetilcolinesterase (AChE). O MFD foi administrado de forma aguda em todos os testes, nas doses de 2,5; 5; 10 e 20 mg/Kg, atravÃs da via oral (v.o.) em camundongos jovens (21 dias) e adultos. Os resultados mostraram que o MFD apresentou efeito ansiolÃtico nos modelos LCE, pois aumentou todos os parÃmetros analisados no LCE, como NEBA, PEBA, TPBA e PTBA nas doses de 10 e 20mg/Kg nos animais jovens e apenas na de 20mg/Kg nos animais adultos. No teste do campo aberto, foi observado aumento na atividade locomotora em todas as doses nos animais jovens e apenas nas doses maiores (10 e 20mg/Kg) nos animais adultos. NÃo alterou o nÃmero de grooming e rearing. O MFD apresentou efeito antidepressivo no Sistema Nervoso Central (SNC), pois no teste do nado forÃado diminuiu o tempo de imobilidade nas doses de 10 e 20 mg/Kg nos animais jovens e apenas na dose de 20mg/Kg nos animais adultos. A avaliaÃÃo neuroquÃmica comprovou o efeito antidepressivo do MFD, pois se verificou um aumento da concentraÃÃo das monoaminas. No teste da convulsÃo induzida por pilocarpina, o metilfenidato diminuiu a latÃncia de convulsÃo, bem como a latÃncia de morte nos animais jovens e adultos, sugerindo que o MFD apresenta atividade proconvulsivante. O estudo sobre os efeitos sobre o sistema de neurotransmissÃo colinÃrgica demonstrou que o prÃ-tratamento com MFD reduziu a atividade da AChE apenas no corpo estriado. Em conclusÃo, esses efeitos mostraram que o MFD apresenta efeito ansiolÃtico, efeito antidepressivo e atividade proconvulsivante.
Attention-deficit hyperactivity disorder (ADHD) is a prevalent and debilitating disorder diagnosed on the basis in persistent levels of overactivity, inattention and impulsivity. Stimulant drugs have been effective in treating this disorder, and methylphenidate (MPH) is the most widely prescribed therapeutic agent and its use has increased significantly in recent years, however, the consequences of its use are still poorly known. The MFD was assessed in classical animal models to the screening of drugs with activity in anxiety, depression and convulsion, such as elevated plus maze (EPM), open field, rota rod, forced swimming and pilocarpine-induced seizures and a neurochemistry study, through the level of monoamines, such as dopamine (DA), norepinephrine (NE) and 5-hidroxytriptamine (5-HT) but the activity of the enzyme acetylcholinesterase (AChE). The MPH was administered acutely in all tests at doses of 2,5; 5; 10 e 20 mg/Kg, through the oral via (p.o.) in young mice (21 days) and adults. Results showed that the MPH presented an anxyolitic effects in the models of EPM, since increased all the parameters analyzed in the EPM, such as NEOA, PEOA, TPOA, PTOA, at doses of 10 and 20 mg/Kg in young animals, and only in animals of 20 mg/Kg in adults. In the open field, we observed an increase in locomotor activity at all doses in young animals and only at higher doses (10 e 20 mg/Kg) in adult animals. Not was observed no alteration the number of rearing and grooming. MPH presented antidepressant effect of Central Nervous System (CNS), since in the forced swimming, decreases the time of immobility in doses of 10 and 20 mg/Kg in young animals and only at a dose of 20 mg/Kg in adult animals. The neurochemistry evaluation comproved the antidepressant effect do MPH, because there was an increased concentration of monoamines. The test of the seizure by pilocarpine, MPH did decrease the latency of convulsion and latency of death in young and adult animals, suggesting that the MPH has proconvulsivante activity. The study of the effects of the cholinergic neurotransmission system has show that pretreatment with MPH reduced AChE activity only in the striatum. In conclusion, these effects showed that MPH presented anxiolitic effect, antidepressant effect and proconvulsivante activity.
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Meschin, Pierre. "Régulations monoaminergiques AMPc-dépendantes du coeur sain et pathologique." Thesis, Montpellier 1, 2014. http://www.theses.fr/2014MON1T010.
Повний текст джерелаАнотація:
La fonction cardiaque est finement régulée par des hormones de type monoamines qui constituent des régulateurs cruciaux de l’activité cardiaque (chronotropie et inotropie). Ces hormones dérivées d’acides aminés aromatiques comprenant les catécholamines et la sérotonine maintiennent l’activité du myocarde dans un cadre physiologique tout en lui permettant de s’adapter aux contraintes environnementales. Les récepteurs cellulaires des monoamines sont couplés à des voies de signalisation qui impliquent un nucléotide cyclique, l’AMPc, et modulent la contractilité des cardiomyocytes par l’intermédiaire de multiples phosphorylations des protéines régulatrices du cycle du calcium (canal calcique de type L, RyR2 ou phospholamban) par la protéine kinase A AMPc-dépendante. Lorsque les monoamines voient leurs activités dérégulées en contextes pathologiques tels que l’insuffisance cardiaque (IC) ou un lors d'un traitement antidépresseur, elles conduisent à une hyperstimulation de leurs récepteurs spécifiques. Cette dernière altère alors les voies impliquant l’AMPc et les flux calciques engendrant des évènements ectopiques proarythmogéniques nommés post-dépolarisations. Ces dysfonctions de la contractilité cellulaire et de l'homéostasie calcique peuvent être à l’origine d’arythmies tissulaires et de morts subites cardiaques. Les altérations de l’homéostasie calcique subsistent en dépit des approches thérapeutiques actuelles (!-bloquants, inhibiteurs de l’enzyme de conversion de l’angiotensine) qui vise à freiner le remodelage myocardique post-ischémique et constituent donc une cible active de la recherche cardiovasculaire. Les Rycals, stabilisateurs pharmacologiques du RyR2, représentent une nouvelle approche visant à remédier à ces altérations. Au sein de ces travaux de recherche, nous avons axé nos études sur les deux voies monoaminergiques AMPc cardiaques majeures, les voies adrénergiques et sérotoninergiques. Un premier axe d’étude a consisté en l’évaluation des bénéfices potentiels d’un nouveau Rycal, le S44121, sur la survenue d’arythmies cellulaires et tissulaires en comparaison d’un !-bloquant de référence, le métoprolol, dans un contexte d’IC post-infarctus chez le rat. L’étude n’a cependant pas mise en évidence de bénéfices du S44121 mais a confirmé la cardioprotection exercée par le métoprolol. Un deuxième axe d’étude a évalué l’implication potentielle au niveau cardiaque de la protéine S100A10 dans la modulation de la voie du récepteur à la sérotonine de type 4 (5-HT4R) en conditions physiologiques ou en contexte d’IC. Cette étude originale a mis en avant pour la première fois dans le coeur sain un rôle de la S100A10 dans l’apparition d’une voie 5-HT4R proarythmogène lorsque son expression est induite par une neurotrophine (Brain-derived neurotrophic factor) ou un antidépresseur (imipramine). En revanche, le rôle de la S100A10 dans la modulation de la voie 5-HT4R en contexte d’IC n’a pas été déterminé de façon certaineCardiac function is tightly regulated by hormones such as monoamines which are substantial modulators of cardiac activity (chronotropy and inotropy). These hormones, derived from aromatic amino acids, maintain myocardial activity in a physiological range and allow the cardiac adaptation to environmental conditions. The cellular receptors to monoamines are coupled to signaling pathways involving a cyclic nucleotide, cAMP, and modulate cardiac activity by phosphorylating several key proteins of calcium handling (L-type calcium channel, RyR2 or phospholamban) by the cAMP-dependent protein kinase A. Deregulation of monoamines in pathological conditions such as heart failure (HF) or during antidepressanttreatment leads to a hyperstimulation of their specific receptors. It therefore induces alterations of the cAMP signaling pathway and calcium handling leading to the occurrence of proarrhythmogenic ectopic cellular events known as afterdepolarizations. These dysfunctions in cellular contractility and calcium handling may cause tissue arrhythmias andeven sudden cardiac death. Calcium handling alterations leading to cardiac arrhythmias remain a clinically relevant issue despite the current therapeutical approaches (!-blockers, angiotensin-converting-enzyme inhibitors) which slow the post-ischemic myocardial remodeling and thus represent an active target in the cardiovascular research field. Rycals, RyR2 pharmacological stabilisers, are a new approach to prevent these alterations. In this work, we focused on the two major monoaminergic cAMP-dependent pathways in the heart, the adrenergic and serotoninergic pathways. In the first part of this work, we aimed to evaluate the potential benefits of a new Rycal, S44121, on cellular and tissue arrhythmias occurrence in post-myocardial infarction rat model. These effects were compared to those of the well-known !-blocker, metoprolol. This study failed to show any strong benefit of S44121 but confirmed the cardioprotection associated with the metoprolol use. In a second part of the work presented here, we aimed to evaluate the potential involvement of the S100A10 protein in the modulation of the cardiac serotonin receptor 4 pathway (5-HT4R) in physiological conditions or during HF. This original study unraveled for the first time a new role for S100A10 in the healthy heart by revealing a functional 5-HT4R pathway when S100A10 expression is induced by neurotrophins such as brain-derived neurotrophic factor or by antidepressant drugs such as imipramine. However, we failed to conclude on a direct evidence for a role of S100A10 in the modulation of the 5-HT4R pathway in the failingheart
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Vacher, Claire-Marie. "Régulation par les monoamines de l'expression de la vasopressine dans l'hypothalamus neuroendocrine : étude cytophysiologique chez la souris Tg8, knock-out pour la monoamine oxydase A (MAO-A)." Paris 6, 2002. http://www.theses.fr/2002PA066359.
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18
Baulieu, Jean-Louis. "Méta-iodobenzylguanidine et captage des monoamines." Tours, 1988. http://www.theses.fr/1988TOUR3302.
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19
Calefi, Atilio Sersun. "Avaliação dos efeitos do estresse por calor sobre a imunidade de frangos de corte em modelos experimentais de enterite necrótica aviária." Universidade de São Paulo, 2016. http://www.teses.usp.br/teses/disponiveis/10/10133/tde-07102016-124200/.
Повний текст джерелаАнотація:
Doenças, como a enterite necrótica aviária (NE), têm se tornado reemergentes em função não apenas do sistema de criação intensivo de frangos de corte atualmente em uso, como também da restrição imposta ao uso dos aditivos antimicrobianos por diversos países, dentre os quais, aqueles da União Européia. A NE é uma doença que acomete aves de produção e seu agente etiológico primário é o Clostridium perfringens tipo A. Pouco se conhece a respeito dos mecanismos pelos quais o estresse modula o desenvolvimento da NE. O presente trabalho foi realizado para avaliar os efeitos do estresse por calor sobre o desenvolvimento da NE em frangos de corte. Empregou-se, para tal, modelos experimentais de NE em que se usou infecção isolada por C. perfringens e/ou em co-infecção com Eimeria spp. O estresse por calor foi aplicado de forma contínua ou intermitente em longo prazo. Foram propostos sete experimentos; em cinco deles os animais foram criados em câmaras isoladoras e, nos dois restantes, em galpões. Foram feitas avaliações da imunidade sistêmica, de órgãos linfoides secundários e do intestino delgado para determinar os efeitos imunomodulatórios da infecção e/ou do estresse por calor. Para caracterização dos efeitos neuroimunes, fizemos uma análise integrada dos achados imunes, de atividade do Sistema Nervoso Central e/ou de ativação do eixo hipotálamo-hipófise-adrenal (HPA). Foram utilizadas medidas quantitativas e semiquantitativas para avaliar os diferentes graus de lesão tecidual decorrentes do processo infeccioso e/ou parasitário com ou sem estresse por calor. Para analisar os efeitos do estresse no processo infeccioso/parasitário empregamos, também, cultivos microbiológicos e técnicas usadas para determinação da proliferação do C. perfringens e da Eimeria spp. Os resultados mostraram que o estresse por calor: reduziu a inflamação intestinal e o dano tecidual em modelo de NE empregando infecção isolada por C. perfringens preparada em caldo tioglicolato; reduziu a formação de centros germinais esplênicos e intestinais com consequente modulação da produção de imunoglobulinas séricas e secretórias; ativou núcleos do SNC relacionados á atividade do eixo HPA; ativou o eixo cérebro-intestinal; diminuiu a infecção intestinal por Eimeria spp., com consequente redução do desenvolvimento da NE e da lesão tecidual dela resultante; modulou a atividade de sistemas de neurotransmissão central relacionados com o comportamento das aves e ativação do eixo HPA; alterou o perfil neuroquímico cerebral quando em associação com a NE; facilitou o desenvolvimento da infecção por C. perfringens em animais não desafiados por fatores predisponentes da NE; reduziu a lesão tecidual no modelo de co-infecção por C. perfringens e Eimeria spp.; modulou o balanço de citocinas para um padrão Th2 no intestino dos animais infectados ou não; alterou as subpopulações de linfócitos esplênicos e circulantes, bem como a função proliferativa destas células e a resposta das mesmas à expressão de citocinas. Desta forma, concluímos que o estresse por calor e/ou inflamação intestinal de origem infecciosa ou química ativam o eixo HPA por mecanismo que envolve o eixo cérebro-intestinal, reduzindo os sinais clínicos da NE por interferir na patogênese do C. perfringens e da Eimeria sppDiseases such as necrotic enteritis (NE) are coming back not only as a consequence of the intensive farming procedures now being used but also as a consequence of the restrictions imposed by the European Union countries to the use of antimicrobials as feed additives. NE is a disease that affects poultry production; its primary etiologic agent is Clostridium perfringens type A. Little is known about the mechanisms by which stress modulates the development of NE. Thus, to evaluate the effects of heat stress on NE development, sevenstudies were done using experimental models of NE that used C. perfringens infection per se or in combination with Eimeria spp. Heat stress was used throughout the experiments, being applied continuously or intermittently but always for long-term. Five experiments were performed using animals reared in isolator chambers and two others employing animals reared in sheds. Evaluations of systemic immunity, secondary lymphoid organs and small intestine portions were used to determine the immunomodulatory effects of the infections and/or of the heat stress. Neuroimmune effects were assessed using an integrative approach of the observed immune, Central Nervous System (CNS) and/or hypothalamic-pituitary-adrenal (HPA) axis changes. Quantitative and semi-quantitative techniques were utilized to measure and compare the different degrees of tissue damage resulting from the infectious processes in the presence and absence of heat stress. Microbiological techniques were also used to determine C. perfringens and Eimeria spp. proliferations. Results showed that heat stress: reduced intestinal inflammation and tissue damage in the NE model that used C. perfringens together with thioglycolate broth culture medium intake; reduced the formation of splenic and intestinal germinal centers with subsequent production of serum and secretory immunoglobulins; activated some brain areas related to animals behavior and HPA axis activity; modified the brain-gut axis relationship during NE development; reduced Eimeria spp. infection leading to a subsequent reduction in the NE development and in the scores of tissue injury; together with NE, modified neuronal brain-amine systems activity and, as a consequence, changed animals behavior, HPA axis activity and brain amine systems fuction within some brain areas; predisposed the birds to C. perfringens infection in the presence or absence of NE inducing factors; reduced the tissue damages observed in the course of C. perfringens and Eimeria spp.co-infection; modulated cytokines to a Th2 pattern in animals infected or not; altered the splenic and peripheral blood lymphocytes subpopulations and, changed the proliferative function of immune cells and cytokine expression.Thus, we conclude that the heat stress and/or intestinal inflammation of infectious or chemical origin activate the HPA axis by a mechanism involving the brain-gut axis, reducing the clinical signs of NE by interfering in the pathogenesis of C. perfringens and Eimeria spp
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Liogier, d'Ardhuy Xavier. "Pharmacologie des potentiels évoqués : influence des monoamines." Lyon 1, 2000. http://www.theses.fr/2000LYO1T112.
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Retailleau, Aude. "Activités normales et pathologiques du réseau hippocampique chez le rat : implication des systèmes monoaminergiques." Thesis, Bordeaux 1, 2011. http://www.theses.fr/2011BOR14405/document.
Повний текст джерелаАнотація:
Les représentations mentales, en particulier les représentations spatiales, sont étroitement associées à l'activation coordonnée de groupes de cellules dans l'hippocampe. Nous avons entrepris l'étude des propriétés et activités spontanées du réseau hippocampique (et plus particulièrement de la région CA3) afin de mieux en comprendre le fonctionnement, dans les situations normales et pathologiques. En effet, certaines pathologies neurodégénératives telle que la maladie de Parkinson serait potentiellement associées à des troubles cognitifs hippocampo-dépendants. Ainsi dans la première partie de ma thèse, nous avons caractérisé la dynamique temporelle des signaux excitateurs et inhibiteurs spontanés de l'hippocampe par une approche électrophysiologique in vitro sur tranches d'hippocampe mais aussi chez l'animal anesthésié grâce des enregistrements multi-unitaires multi-sites. Ces travaux nous a permis de mettre en évidence que les caractéristiques de la dynamique du réseau CA3 remplissent quelques critères essentiels au concept d'assemblées cellulaires. De plus, cette étude a mis en évidence les caractéristiques fonctionnelles de l'hippocampe chez l'animal normal. Ces résultats peuvent donc être utiles pour de futures études sur les pathologies hippocampo-dépendantes touchant le codage ou la mémoire spatiale telle que la maladie de Parkinson. Ainsi, dans la deuxième partie de ma thèse, nous avons étudié les altérations fonctionnelles du circuit hippocampique chez un modèle rat de la maladie de Parkinson. La maladie de Parkinson est une maladie neurologique qui affecte le système nerveux central et entraine des symptômes essentiellement moteurs. La cause est une dégénérescence des neurones dopaminergiques mais aussi noradrénergiques et sérotoninergiques. Cependant, en dehors des troubles moteurs, cette pathologie est aussi caractérisée par des troubles cognitifs notamment des déficits spatiaux. Notre projet a donc consisté à analyser les mécanismes par lesquels les déplétions monoaminergiques entraîneraient des troubles de l'apprentissage spatial. Ce travail a été réalisé chez le rongeur à l'aide d'une étude associant une approche comportementale et des enregistrements électrophysiologiques chez l'animal anesthésié mais aussi chez l'animal éveillé en comportement. Nous avons ainsi pu mettre en évidence des dysfonctionnements hippocampiques causés par des lésions contrôlées des différents systèmes mono-aminergiques (plus particulièrement dopaminergique et noradrenergique) impliqués dans la maladie de ParkinsonMental representations, especially spatial ones are closely related to correlated activity in cellular assembly in the hippocampus. In this work, we analyzed the properties and the spontaneous activity of the hippocampal network in order to unravel its functioning in normal and pathological conditions. Several neurodegenerative disorders such as Parkinson's disease seems to be also associated to cognitive disorder related to hippocampus dysfunction. We first characterized the temporal dynamic properties of spontaneous excitatory and inhibitory signal. We then studied the functional alteration of the hippocampal network in a rat model of Parkinson's disease using behavioral and electrophysiological investigations. Our work showed that controlled lesion of the various monoaminergic systems induced hippocampus dysfunction related to spatial disorientation.In the first part of my thesis, we characterized the temporal dynamic of excitatory and inhibitory signals with electrophysiological recordings in vivo on hippocampal slices but also in anesthetized animals with multi-units multi-sites recordings. These studies allowed us to highlight that dynamic of CA3 network meets the criteria of cells assembly concept. Moreover, we characterize the functional properties of hippocampus in physiological conditions. These results could be useful for further studies on hippocampo-dependant pathologies in the context of spatial coding and memory.Thus, in the second part of my work, we studied the functional alterations of hippocampal network in the context of Parkinson disease. This pathology is a neurodegenerative disease which affects the central nervous system and leads essentially to motor symptoms. The cause is the degeneration of dopamine neurons but also of noradrenalin and serotonin neurons. Nevertheless, this pathology is also associated to cognitive disorders notably a form of spatial disorientation. Our project consisted to analyze the mechanisms by which monoamines depletions led to spatial learning impairments. This work was realized on rats with a study combinating behavioral approach with electrophysiological recordings in anesthetized animals but also in awake animals. We showed that some monoamines depletions (and notably dopamine and noradrenalin depletions) led to spatial impairments in behavioral tasks correlated to a change in firing and coding of neurons of hippocampus
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Mullan, Elaine L. "Inhibitors of monoamine oxidase." Thesis, Queen's University Belfast, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337116.
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DESNOS, CLAIRE. "Regulation de l'expression du transporteur vesiculaire des monoamines." Paris 6, 1992. http://www.theses.fr/1992PA066452.
Повний текст джерелаАнотація:
La stimulation prolongee des cellules chromaffines provoque une augmentation de l'expression de certains enzymes de biosynthese des catecholamines et constituants des granules de secretion. Afin d'etudier cette induction trans-synaptique in vitro il est possible de stimuler de facon prolongee les cellules chromaffines bovines en culture en les depolarisant dans un milieu riche en potassium. Nous nous sommes interesses a l'expression d'une proteine de la membrane granulaire, le transporteur vesiculaire des monoamines, responsable de l'accumulation des catecholamines dans les granules de secretion. Le transporteur vesiculaire des monoamines est dose en utilisant un ligand specifique, la (#3h) dihydrotetrabenazine. Nos resultats indiquent qu'une entree de calcium dans les cellules chromaffines provoque une induction specifique de l'expression de transporteur, probablement par activation de sa neosynthese. Nous avons egalement observe, en collaboration avec m. Weber, qu'il existait une regulation du transporteur vesiculaire des monoamines dans les neurones sympathiques de ganglion cervical superieur de rat nouveau-ne en milieu depolarisant. Par la suite, notre objectif a ete de mieux comprendre les consequences d'une secretion soutenue et notamment de localiser sur quel type de vesicules se situait le transporteur induit. L'etude de la localisation subcellulaire montre que dans ces conditions de stimulation prolongee, les cellules chromaffines restent capables de secreter et accumulent des precurseurs de granules dont la composition membranaire et matricielle est modifiee
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Raucoules, Daniel. "Catabolites plasmatiques des monoamines et depressions : etude preliminaire." Aix-Marseille 2, 1989. http://www.theses.fr/1989AIX20954.
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Garraway, Sandra Mary. "Monoamines and the modulatory control of spinal sensory processing." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0011/NQ53057.pdf.
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26
Branger, Caroline. "Développement de molécules pour l'exploration des transporteurs des monoamines." Tours, 1995. http://www.theses.fr/1995TOUR3305.
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Franzén, Louise. "Manipulation of monoamines and effects on behavior in crickets." Thesis, Umeå universitet, Institutionen för ekologi, miljö och geovetenskap, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-140444.
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Wragg, Rachel T. "Monoamines and Peptides Interact to Inhibit Glutamatergic Signaling in Caenorhabditis elegans." University of Toledo / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=toledo1279208105.
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29
Fitzgerald, Julia. "Monoamine oxidase in neuronal cell death." Thesis, Nottingham Trent University, 2008. http://irep.ntu.ac.uk/id/eprint/51/.
Повний текст джерелаАнотація:
Monoamine oxidase (MAO) is an oxidative enzyme that deaminates a variety of amine substrates, including the neurotransmitter dopamine. The enzymatic reaction requires molecular oxygen and produces hydrogen peroxide as a by-product. MAO is localised in the outer mitochondrial membrane and exists as two isoforms, MAO-A and MAO-B, which are differentially expressed in the body and differ in their substrate and inhibitor specificities. Previous studies have suggested that MAO-generated reactive oxygen species (ROS) contribute to oxidative stress in the cell and can directly inhibit electron transport, cause damage to mitochondrial DNA and enhance cell death signalling. In this study the role of MAO in cell death was investigated in dopaminergic neuroblastoma (SH-SY5Y) cells, in three diverse models of mitochondrially-mediated apoptosis. The relevance of MAO in cell death signalling was confirmed with the use of two unrelated MAO inhibitors and the creation of stable SH-SY5Y cell lines that either over express MAO-A or have reduced levels of MAO-A. The study is the first to over express MAO-A using recombinant technology and to use miRNA to stably knock-down MAO-A expression in human neuronal cells. Results confirm that MAO-A is involved in modulating cell death but the mechanism and extent of the involvement depends on the apoptotic inducer. In classical apoptosis induced by staurosporine (STS), cells undergo rapid morphological and biochemical changes indicative of mitochondrially-mediated apoptosis, which is partly dependent on ROS production by MAO-A and induction of mitogen-activated protein kinase (MAPK) signalling cascades. MAO-A protein and catalytic activity are increased in this model, however the mechanism by which this occurs is unknown and is not a result of increased gene transcription. In death induced by growth factor withdrawal, the MAO-A gene is up regulated via p38 and JNK MAPK pathways, which occurs downstream of caspase activation. In both the STS and growth factor withdrawal models, MAO inhibition reduced apoptosis. Most significantly reduced levels of MAO-A expression in 'knock down' cells protected against cell death induced by the complex I inhibitor rotenone, suggesting that MAO has an important role in mitochondrial function. Over expression of MAO-A resulted in stress and apoptosis, followed by a period of cellular senescence and eventually death by necrosis. These data compliment the effects of chronic exposure to oxidative stress in ageing and neurodegeneration. For the first time this work has shown that the MAO-A isoform is an important regulator of STS-induced apoptosis, that MAO-A gene expression is regulated by JNK signalling, and that MAO-A is significantly involved in mitochondrial dysfunction induced by complex I inhibition. These data raise important questions regarding predisposition to the development of neurodegenerative diseases such as Parkinson's disease and to approaches used for their treatment.
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Stenström, Anders. "Intra- and extraneuronal monoamine oxidase (MAO)." Umeå : [University of Umeå], 1986. http://catalog.hathitrust.org/api/volumes/oclc/15239401.html.
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Kindt, Katherine. "Monoamines, mechanosensation and memory in the C. elegans nervous system." Connect to a 24 p. preview or request complete full text in PDF format. Access restricted to UC campuses, 2006. http://wwwlib.umi.com/cr/ucsd/fullcit?p3232323.
Повний текст джерелаАнотація:
Thesis (Ph. D.)--University of California, San Diego, 2006.Title from first page of PDF file (viewed December 4, 2006). Available via ProQuest Digital Dissertations. Vita. Includes bibliographical references.
32
Smounya, Larbi. "Prostaglandines et monoamines cerebrales chez la souris et le rat." Besançon, 1993. http://www.theses.fr/1993BESA3716.
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33
Yeomanson, K. B. "An immunochemical analysis of monoamine oxidase profiles." Thesis, Nottingham Trent University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.254741.
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34
Maurel, Agnès. "Monoamine oxydases rénales et cardiaques : implications physiopathologiques." Paris 7, 2004. http://www.theses.fr/2004PA077127.
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35
Wu, Bo. "Structure-function relationships in monoamine oxidase B /." Digital version accessible at:, 1998. http://wwwlib.umi.com/cr/utexas/main.
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36
Ruchala, Iwona. "EXPANDING MONOAMINE TRANSPORTERS PHARMACOLOGY USING CALCIUM CHANNELS." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/5032.
Повний текст джерелаАнотація:
Research in drug development meets many challenges including lengthy, complex and costly procedures to identify novel pharmacotherapies. In our lab, we developed a method for fast screening of small molecules that interact with monoamine transports – dopamine and serotonin (DAT, SERT). These membrane proteins play important roles in brain neurotransmission responsible for cognition, motion and pleasure. Dysfunction in dopaminergic and serotonergic systems result in neurological disorders such as depression, Attention Deficit Hyperactivity Disorder (ADHD), schizophrenia and addiction.
DAT and SERT are responsible for uptake of dopamine (DA) or serotonin (5HT) into the synapse and they limit neurotransmitter signaling. Drugs that mimic or antagonize actions of endogenous neurotransmitters (DA and 5HT) increase the concentrations of DA and/or 5HT either by blocking the transporter (blockers) or by competing uptake with neurotransmitter (substrate). The uptake of substrates is associated to an inward current that depolarizes the cell membrane. Voltage-gated calcium channels (CaV) can respond to small changes in membrane potential. In our method, we combined permanent cell line expressing the human dopamine transporter (hDAT) or the human serotonin transporter (hSERT) (FlpIn TREx expression system) with transient transfection of CaV. This system works as a tightly electrically coupled system. Cells challenged with substrate of the transports produce detectable Ca2+ signal while monoamine transporter blockers can inhibit these Ca2+ signals. The novelty of this method relies on the ability to discriminate between substrate and blockers of monoamine transporters.
Preliminary experiments measuring our optimized cell system in a Flex Station 3 plate reader suggest that the co-expression of a voltage-gated Ca2+ channel, a monoamine transporter and a genetically encoded Ca2+ sensor constitute a rapid screening biosensor to identify active drugs at monoamine transporters.
Our novel methodology can rapidly assess drug-effect profile on monoamine transporters and benefit development of new psychotherapeutics for treatment of mental illnesses. It can also be used to characterize mechanism of action of emerging drug of abuse, as well as to discover small molecules with novel drug-effect profile useful in basic neuroscience research.
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Saiyudthong, Somrudee. "Mechanisms underlying the antidepressant properties of St. John's wort (Hypericum perforatum)." Thesis, University of Nottingham, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.275319.
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Chernoloz, Olga. "Reciprocal Interactions Between Monoamines as a Basis for the Antidepressant Response Potential." Thesis, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/22663.
Повний текст джерелаАнотація:
Despite substantial progress in the area of depression research, the current treatments for Major Depressive Disorder (MDD) remain suboptimal. Therefore, various medications are often used as augmenting agents in pharmacotherapy of treatment-resistant MDD. Despite the relative clinical success, little is known about the precise mechanisms of their antidepressant action.
The present work was focused on describing the effects of three drugs with distinctive pharmacological properties (pramipexole, aripiprazole, and quetiapine) on function of the monoaminergic systems involved in the pathophysiology and treatment of MDD. Reciprocal interactions between the monoamines serotonin, norepinephrine, and dopamine systems allow the drugs targeting one neuronal entity to modify the function of the other two chemospecific entities.
Electrophysiological experiments were carried out in anaesthetized rats after 2 and 14 days of drug administration to determine their immediate and the clinically-relevant long-term effects upon monoaminergic systems.
Pramipexole is a selective D2-like agonist with no affinity for any other types of receptors. It is currently approved for use in Parkinson’s disorder and the restless leg syndrome. Long-term pramipexole administration resulted in a net increase in function of both dopamine and serotonin systems.
Aripiprazole is a unique antipsychotic medication. Unlike all other representatives of this pharmacological class that antagonize D2 receptor, this drug acts as a partial agonist at this site. Chronic administration of aripiprazole elevated the discharge rate of the serotonin neurons, presumably increasing the overall serotonergic neurotransmission.
Like aripiprazole, quetiapine is one of three atypical antypsicotic drugs approved for use in MDD. Prolonged administration of quetiapine led to a significant increase in both noradrenergic and serotonergic neurotransmission. Importantly, the clinically counter-productive decrease in the spontaneous firing of catecholaminergic neurons, induced by SSRIs, was overturned by the concomitant administration of both aripiprazole and quetiapine.
The increase in serotonergic neurotransmission was a consistent finding between all three drugs studied herein. In every case this enhancement was attained in a distinctive manner. Understanding of the precise mechanisms leading to the amplification/normalization of function of monoamines enables potential construction of optimal treatment strategies thereby allowing clinicians greater pharmacological flexibility in the management of depressive symptoms.
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Iken, Khadija. "Mécanismes de régulation de la prolifération des lymphocytes B par les monoamines." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/NQ65358.pdf.
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Tunon, de Lara José-Manuel. "Influence des immunoglobulines E sur la captation plaquettaire des monoamines chez l'homme." Bordeaux 2, 1989. http://www.theses.fr/1989BOR25203.
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CUSSEY, JACQUES. "Approche biologique de la depression : recherche de marqueurs biologiques (monoamines, endocrinologie, immunite)." Besançon, 1991. http://www.theses.fr/1991BESA3706.
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Sagné, Corinne. "Etude du transporteur vesiculaire des monoamines : purification et caracterisation de domaines fonctionnels." Paris 6, 1997. http://www.theses.fr/1997PA066173.
Повний текст джерелаАнотація:
Dans les neurones monoaminergiques et certaines cellules endocrines, les monoamines sont accumulees dans des organites specialises, permettant leur liberation par exocytose lors d'une stimulation de ces cellules. L'accumulation est due a un antiport proton/monoamine dont est responsable le transporteur vesiculaire des monoamines (vmat), qui utilise le gradient electrochimique de protons transmembranaire cree par une atpase translocatrice de protons. Le transporteur est inhibe selectivement par la reserpine, la tetrabenazine et la ketanserine. Nous nous sommes attaches a caracteriser la structure de vmat. Tout d'abord, nous avons mis au point une technique de purification originale, par agregation selective, de l'isoforme vmat2, majoritaire dans les granules de la medullo-surrenale bovine. Cette methode est susceptible d'etre appliquee a d'autres proteines membranaires. L'etude de l'agregation nous a egalement permis de proposer qu'il existe des structures secondaires extremement stables dans vmat2 qui ne peuvent etre denaturees que par l'acide trifluoroacetique anhydre. Ensuite, nous avons localise un domaine de liaison de la ketanserine sur la sequence primaire de vmat2 a l'aide d'un derive photoactivable, l'azik. En combinant le sequencage de peptides derives du transporteur purifie a la mutagenese dirigee d'un site de proteolyse de vmat2, nous avons montre que l'azik se fixe sur son domaine n-terminal, precisement entre les residus 2 et 55 (sur 518 acides amines). Enfin, nous avons initie une etude experimentale de la topologie de vmat2 par traduction in vitro en utilisant des sites de glycosylation comme rapporteurs de topologie. D'autre part, la mutagenese des extremites n- et c-terminales de bvmat2 semble indiquer qu'elles ne participent pas a l'activite de transport.
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RAFII, HAMID. "Developpement de ligands radioactifs pour l'exploration des monoamines oxydases cerebrales en tomoscintigraphie." Paris 11, 1996. http://www.theses.fr/1996PA112080.
Повний текст джерелаАнотація:
Les monoamines oxydases (mao-a et mao-b) sont importantes dans la regulation de la neurotransmission monoaminergique. Des perturbations de l'activite de ces enzymes ont ete observees dans des affections psychiatriques et neurodegeneratives. Par ailleurs, la quantification des mao cerebrales pourrait permettre le diagnostic de ces affections et eventuellement, le suivi therapeutique sous l'effet des traitements. Dans le but d'une exploration scintigraphique des mao in vivo en spect, nous avons entrepris de synthetiser des radioligands ayant des proprietes inhibitrices de ces enzymes a l'iode radioactif. Au cours de ce travail, nous avons developpe dans la premiere partie les generalites sur les mao et leurs inhibiteurs. La deuxieme partie est consacree a la description des techniques scintigraphiques, des radioligands susceptibles pour l'exploration des mao, et des methodes de marquage a l'iode radioactif. En fin dans la troisieme partie nous avons developpe trois radioligands: la #1#2#5i3-iodopargyline. Les premiers resultats obtenus in vivo chez le rat indiquent que ce compose inhibe la mao-b cerebrale avec une selectivite moderee. Cependant, des etudes complementaires sont necessaires afin de preciser l'activite de ce radioligand in vivo. Le #1#2#5iro 16-6491. La fixation cerebrale de ce compose correspond aux sites de la mao-b. Cependant, cette fixation semble trop faible pour une exploration scintigraphique in vivo. Le #1#2#5iro 11-9900. Les resultats obtenus in vivo montrent que ce radioligand est un inhibiteur preferentiel des sites de la mao-a dans le cerveau. L'etude de la biodistribution cerebrale de ce compose marque a l'iode 123 est envisageable dans le singe
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Rezai, Amin Sara. "Rôle du transporteur plasmique des monoamines (PMAT) dans le système nerveux central." Thesis, Sorbonne Paris Cité, 2017. http://www.theses.fr/2017USPCC247.
Повний текст джерелаАнотація:
Dans le système nerveux central, les monoamines modulent de nombreuses fonctions essentielles comme la locomotion, la motivation, la cognition, l’humeur et le sommeil. Le niveau extracellulaire de ces neurotransmetteurs est régulé par des transporteurs à haute affinité,cependant d’autres transporteurs, à faible affinité, peuvent contribuer à la recapture des monoamines, comme les transporteurs de cations organiques (OCT) et le transporteur plasmique des monoamines (PMAT). Récemment, l’implication des OCT dans différentes fonctions centrales, notamment le contrôle de l’humeur, la réponse au stress et aux antidépresseurs a été mise en évidence. Le rôle de PMAT dans le cerveau reste quant à lui encore peu caractérisé. Il transporte in vitro les monoamines, avec une préférence pour la dopamine et la sérotonine, avec des affinités submillimolaires. Ce transporteur est exprimé dans de nombreuses régions du cerveau humain et murin et dans différents types neuronaux. Par hybridation in situ fluorescente nous avons déterminé sa distribution cellulaire précise, dans des régions à fort niveau d’expression comme le complexe du cerveau antérieur basal (BFC) et des régions appartenant aux ganglions de la base comme le globus pallidus et la substance noire réticulée (SNr). Nous avons montré qu’il est fortement exprimé dans les neurones GABAergiques exprimant la parvalbumine, dans tous les interneurones cholinergiques dustriatum ainsi qu’une petite fraction des neurones cholinergiques du BFC. Il est également retrouvé dans certains noyaux monoaminergiques comme le locus coeruleus et les noyaux duraphé mais est absent des noyaux dopaminergiques, la substance noire compacte et l’aire tegmentale ventrale.Afin d’étudier sa fonction, nous avons exploité le système Cre-lox, approche couramment utilisée en biologie, en injectant un virus adéno-associé exprimant la recombinase Cre (AAVCre)dans la substance noire (SN) de souris comportant des allèles de PMAT floxés. Cette étude ne nous a pas permis de conclure quant à la fonction de PMAT dans la SN, mais nous a conduit à mettre en évidence une toxicité majeure de cet outil. Nous avons montré que l’injection d’AAV-Cre dans la SN entraine une perturbation anatomique et fonctionnelle des systèmes dopaminergiques et de la SNr, noyau de sortie des ganglions de la base, induisant des altérations comportementales importantes, avec une hyperlocomotion basale robuste et une insensibilité à la cocaïne, potentiellement par une action génotoxique.Nous avons également généré des souris invalidées constitutivement pour PMAT (PMAT-/-). Les tests comportementaux que nous avons commencés récemment nous ont révélé des altérations comportementales significatives chez ces souris de l’activité locomotrice dans un nouvel environnement ainsi que du niveau d’anxiété. Ces altérations pourraient résulter d'une perturbation des voies aminergiques en l’absence de PMAT. Nous poursuivrons cette étude par l'exploration d'autres aspects comportementaux ainsi que par l’évaluation des modifications neurochimiques engendrées par l'invalidation. Ces approches devraient fournir des pistes afin d’identifier les conséquences de l'absence de PMAT sur la signalisation aminergique, que l'on pourra explorer plus précisément par la suite sur le plan fonctionnelHigh-affinity reuptake transporters exert a crucial role in the control of synaptic transmissionby ensuring the recycling of the released transmitters into the presynaptic terminals. Other typesof transporters such as Organic Cation Transporters (OCTs) and the Plasma MembranemonoAmine Transporter (PMAT), have been shown to transport, with low-affinity but highcapacity, aminergic neurotransmitters. While the role of OCTs in central nervous system hasbeen partially unraveled, the function of PMAT remains poorly characterized. In vitro, PMATtransports preferentially dopamine and serotonin and its expression is widespread in the brain,encompassing monoamine nuclei but also projection regions. In this study, we determined theprecise neuronal specificity of PMAT in several highly-expressing regions. We show that it isfound mostly in PV+ GABAergic neurons of basal forebrain and basal ganglia, in allcholinergic interneurons of the striatum and in some cholinergic neurons of basal forebraincomplex. These systems, highly regulated by monoamines, are important for locomotion,motivation, learning and wakefulness. Our result show that PMAT is located at a strategicposition to control the aminergic modulation of these integrated functions.To investigate the implication of PMAT in these regions, we used the Cre-lox technology, avalued and widely used approach for the study of gene function in vivo, injecting an adenoassociatedvirus expressing Cre recombinase in substantia nigra (SN) of mice in which PMATgene was floxed. In this study, we could not assess PMAT function in this SN but found thatAAV-CRE expression in this region produces major toxic effects. We showed that AAV-Creinjection in this region engenders a massive decrease of neuronal populations in both parscompacta and reticulata, leading to DA depletion in the nigrostriatal pathway. This wasassociated with a drastic behavioral phenotype with increased basal locomotor activity and lossof locomotor response to cocaine. Several hallmarks of Cre toxicity were found in SN of AAVCreinjected mice, including an increase of the DNA break markers. These observationsunderscore the need for careful control of Cre toxicity in the brain and reassessment of previous studies.To study the role of PMAT, we also generated PMAT knock out mice (PMAT-/-). Behavioralstudies that we just started have revealed significant impairments of locomotor activity in a newenvironment and anxiety level, supporting a possible disruption of monoaminergic systems inthese mice. On-going studies aim to explore other behaviors and search for eventualneurochemical changes provoked by PMAT invalidation. These experiments should providesome cues to understand which monoamines and circuits may be affected, that can beinvestigated functionnally and more specifically in a second step
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Foka, Germaine Boulenoue. "Synthesis and evaluation of novel coumarin-donepezil derivatives as dual acting monoamine oxidase B and cholinesterase in Alzheimer's disease." University of the Western Cape, 2016. http://hdl.handle.net/11394/5549.
Повний текст джерелаАнотація:
Magister Pharmaceuticae - MPharmAlzheimer's disease is a progressive neurodegenerative disease characterised by low acetylcholine (ACh) levels in the hippocampus and cortex of the brain, causing symptoms like progressive memory loss, decline in language skills and other cognitive impairments to occur. The hallmarks of AD include the presence of extracellular insoluble amyloid beta plaques, intracellular neurofibrillary tangles, and the decrease in ACh concentration. The pathophysiology of AD is not well understood, however, acetylcholinesterase (AChE), butyrylcholinesterase (BuChE) and monoamine oxidases (MAO) are conspicuous role players in AD pathogenesis. Based on the cholinergic hypothesis, the AChE inhibitor donepezil was developed and has been used effectively clinically in the management of AD, with minimal side effects. Studies regarding the binding interactions of donepezil with AChE has shown that the benzyl-piperidine moiety of this compound shows substantial binding interactions at the CAS site of AChE where it blocks AChE activity. Coumarin is a compound of natural source that has shown some MAO inhibitory activity. Further studies done to clarify the potential of coumarin as a drug against AD has shown that coumarin has the capacity to bind at the PAS site of AChE, thus giving it the potential to prevent AChE induced amyloid plaque formation. Due to the multifactorial nature of AD, the drugs in the market show limited therapeutic benefits and are mainly for symptomatic relief. In order to address this limitation in AD treatment, researchers are exploring the possibility of designing a multi-target-directed-ligand (MTDL). The aim of this study was to synthesise a series of compounds out of pharmacophoric groups of donepezil and coumarin that will be able to inhibit both cholinesterases and MAO B. Four series of 5 compounds per series were synthesised. The first series of compounds consisted of the coumarin moiety to which a 1,4-dibromo benzene moiety was attached. The second series represented the coumarin moiety to which a piperidine (donepezil moiety shown to confer cholinesterase inhibitory property) was attached. The third series represented the coumarin moiety to which bromobenzyl-piperazine was attached and in the last series were compounds similar in structure to series 1 with an unsubstituted benzyl moiety as opposed to the dibromobenzyl moiety. Prior to the synthesis, molecular modelling was conducted in order to have an idea of the binding capacity of the compounds to MAO A and B and cholinesterases. In vitro biological evaluation of the compounds was done and used to determine the IC₅₀ values of the compounds. Nineteen compounds were synthesised and purified successfully as shown by their NMR, MS and IR spectra. The compounds to which dual inhibitory activity was conferred were those in series 2 and 3, of which series 2 showed the best overall inhibitory activity with IC₅₀ values within the low μM range. The compound with the best overall activity was Cp 9. Molecular modelling of Cp 9 showed that the coumarin core was located in the PAS region of AChE while the benzyl-piperidine moiety was situated in the CAS region of the enzyme. This compound orientation demonstrates the potential of Cp 9 to inhibit AChE induced amyloid beta plaque formation. Cp 9 showed no inhibitory activity towards MAO A, but showed good inhibitory activity towards MAO B with an IC₅₀ value of 0.30 μM. Its inhibitory activity towards cholinesterases also fell within the low μM range (AChE IC50 = 9.1 μM and BuChE IC₅₀ = 5.9 μM). From the results, it can be concluded that Cp 9 was able to inhibit both cholinesterase and MAO B catalytic activities at low μM concentrations. This thus means that our novel compound will not only increase ACh levels in the brain thus improving cognitive activity, but it will also have neuroprotective effect from its MAO B inhibitory property and also potentially slow down amyloid plaque formation due to AChE activity.
National Research Foundation (NRF)
46
Backwell, Colette. "Labels for the active site of monoamine oxidase." Thesis, Queen's University Belfast, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.336043.
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47
Abdel-Razaq, Wesam. "Molecular mechanisms of monoamine neurotransmitter modulatory antidepressant actions." Thesis, University of Nottingham, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435767.
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48
Jackson, Gillian. "Monoamine release and turnover in broiler chicken brain." Thesis, University of Bristol, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.411086.
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49
Vince, Matthew Joseph Kline. "Examining Monoamine Oxidase Inhibitor Targets Using Caenorhabditis elegans." Ohio University Art and Sciences Honors Theses / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=ouashonors1598384776888279.
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Fournet, Vincent. "Caractérisations biochimique anatomique et comportementale des souris dépourvues de la protéines STOP : un modèle expérimental pour l'étude de symptômes psycho-affectifs." Phd thesis, Université de Grenoble, 2011. http://tel.archives-ouvertes.fr/tel-00656067.
Повний текст джерелаАнотація:
La protéine STOP (MAP6) associée aux microtubules joue un rôle clé dans l'architecture neuronale et la plasticité synaptique, dont les dysfonctionnements sont considérés comme étant impliqués dans la physiopathologie des maladies psychiatriques. En accord avec cette hypothèse, la délétion de la protéine STOP chez la souris, conduit à des altérations neuroanatomiques, biochimiques et comportementales, en partie atténuées par des traitements antipsychotiques. Dans cette étude, nous avons tout d'abord examiné les possibles altérations des systèmes monoaminergiques chez les souris STOP KO. Chez les souris mutantes, les marqueurs sérotoninergiques et noradrénergiques sont accumulés dans le mésencéphale et, au contraire fortement diminués dans toutes les régions de projections du cerveau antérieur. De plus, ces déséquilibres monoaminergiques sont associés à une augmentation du statut dépressif, une diminution du statut anxieux et des déficits dans des tâches d'apprentissage et de mémorisation. Les effets d'un traitement chronique par la fluoxétine ou par l'épothilone D, un composé analogue du taxol stabilisant les microtubules, sur l'humeur et les performances cognitives des souris STOP KO ont aussi été évalués. Le traitement chronique par la fluoxétine induit des effets paradoxaux sur le statut dépressif et le statut anxieux des souris STOP KO suivant les tests effectués, probablement à cause d'une hypersensibilité au stress. En revanche, les traitements chroniques à la fluoxétine et à l'épothilone D ont amélioré la mémoire à court terme des souris STOP KO. Dans l'ensemble, ces résultats indiquent que la délétion de la protéine STOP chez la souris induit de fortes altérations de l'humeur et des performances cognitives et que la protéine STOP pourrait avoir un rôle crucial dans le développement des systèmes monoaminergiques.