Tesis sobre el tema "Modélisation des maladies neurodégénératives"
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Lemonnier, Thomas. "Modélisation de maladies neurodégénératives à l’aide de cellules souches pluripotentes induites humaines". Thesis, Paris 5, 2012. http://www.theses.fr/2012PA05T074/document.
Texto completoReprogramming technology of somatic cells in induced pluripotent stem cells (iPS) now offers the opportunity to model neurodegenerative diseases and to study patient’s neurons. We used this technology for generating two models of neurodegenerative diseases: the muccopolysaccharidosis type IIIB (MPSIIIB) and the ALS2 form of amyotrophic lateral sclerosis (ALS). In the MPSIIIB model, we have shown that iPS and neurons of patients had characteristic defects of the disease such as the accumulation of storage vesicles. Alterations of the Golgi apparatus in these cells were also highlighted. Transcriptome analysis of MPSIIIB neural precursors showed transcriptional changes involving particularly genes implicated in cell-extracellular matrix interactions. Thus, in a subsequent study, alterations of migration and orientation of MPSIIIB mutant mouse cells and MPSIIIB patients’ cells have been demonstrated. These alterations may be responsible for the disruption of neurogenesis and neuritogenesis in sick children. In the ALS2 model, we have shown that patients’ neurons had defects including decreased endosomes’ surface and abnormal neurite outgrowth. As there was previously no relevant cellular model reproducing the disease, this model will now allow the study of physiopathological processes involved in the disease. In conclusion, the generation of iPS cells allows to model neurodegenerative diseases and to study associated physiopathological processes on cultured human neurons. These cell models could allow in the near future the screening of molecules of potential therapeutical interest
Lemonnier, Thomas. "Modélisation de maladies neurodégénératives à l'aide de cellules souches pluripotentes induites humaines". Phd thesis, Université René Descartes - Paris V, 2012. http://tel.archives-ouvertes.fr/tel-00806699.
Texto completoHaffaf, Hadjer Wafaa. "Analyse de l'agrégation des protéines dans les maladies neurodégénératives amyloïdes : application aux maladies à prion". Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066263/document.
Texto completoThe amyloid neurodegenerative diseases are characterized by the degeneration and the aggregation of specific proteins. These aggregation processes remain misunderstood by specialists and, mostly, only hypothetical. In this thesis, and in collaboration with biophysicists, we analyze the mechanisms of aggregation, relying on experimental data. Modeling is then a must. We present two models which we compare with the experiments. The first model, well-known from the literature is the Becker-Döring system. An infinite system of ordinary differential equations. This first model allows us to reproduce satisfactorily the early stages of the experiments. The second model we introduce is based on an additional hypothesis which is about the formation of different fibers. This second model allows us to reproduce the experiments
Sivera, Raphaël. "Modélisation et mesure de l'évolution morphologique du cerveau à partir d'IRM structurelles pour l'étude des maladies neurodégénératives". Thesis, Université Côte d'Azur (ComUE), 2019. http://www.theses.fr/2019AZUR4082.
Texto completoIn medical imaging, the statistical analysis of deformations enables the characterization of the effects of neurodegenerative diseases on the brain morphology. Deformations are able to capture precise changes but their analysis raises specific methodological challenges and the results may be difficult to interpret. The objective of this thesis is to present deformation-based methods and to show applications that contribute towards a better clinical interpretation of morphological changes. In the first part, we introduce a joint model of the effects of normal aging and Alzheimer’s disease on the brain morphology. The model proposes a simple description of both processes and is used to generate realistic and personalized evolutions under several diagnosis conditions. In the second part, a morphometric study is conducted on the MAPT cohort. We bring out an effect of the multidomain intervention on the longitudinal deformation of the brain using multivariate statistics. This effect is not observable using clinical assessments or volumetric measures, but we show that the differences associated with the treatment are correlated with better cognitive performance. The third part extends the statistical methodology used in the second part. A complete hypothesis testing framework for multivariate images is presented. It generalizes existing non-parametric frameworks and requires few hypothesis on the data to be applied. Finally the last part builds on the methodology of the previous sections to explore the relation between morphology and cognition in elderly subjects. The spatial correlations and the patterns of evolution described in this section suggest the existence of several dynamics of evolutions that are associated with specific cognitive changes
Sauty, Benoît. "Multimodal modelling of Alzheimer's Disease progression". Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS348.
Texto completoAlzheimer's disease (AD) is a multi-facet pathology, that can be monitored through a variety of data types. This thesis aims to leverage multimodal longitudinal data, especially imaging scans and cognitive tests, to provide a statistical description of the progression of AD and to enable individual forecasting of future decline. Mixed-effect disease progression models (DPMs) are commonly used for these tasks. In this context, our first contribution questions the frequent assumption that biomarkers follow linear or logistic functions over time, and we propose a geometric framework that assumes the data lie on a manifold and follow geodesics over time. We learn the Riemannian metric of the observation space and are able to model a wider variety of biomarkers, without priors on the shape of the trajectory over time. Using variational auto-encoders, we then extend this framework to neuroimaging data (MRI or PET scans), in order to provide high-dimensional progression models that describe the patterns of structural and functional alterations of the brain over the course of AD. We then apply this family of DPMs to clinical studies data in order to investigate the heterogeneity of AD progression, due to APOE-e4 genotype and sex on patterns of brain alterations. Lastly, we use said DPMs with a set of imaging and fluid biomarkers to identify the specific combinations of input features that best forecast cognitive declines in patients at different stages of the disease. The thesis demonstrates that DPMs can effectively model the progression of AD using a great variety of multimodal longitudinal data and provide valuable insights into the disease's clinical manifestations and progression. These findings can inform clinical trial design and facilitate more accurate prognosis and individualized treatment strategies for patients with AD
Gay, Marion. "Conception, synthèse et évaluation de composes interagissant avec la dégradation des protéines pour le traitement de maladies neurodégénératives". Thesis, Lille 2, 2015. http://www.theses.fr/2015LIL2S056.
Texto completoTwo physiopathological processes are involved in Alzheimer’s disease: the senile plaques (amyloid pathology) consisting of Aβ peptide aggregates and neurofibrillary tangles (Tau pathology) caused by the accumulation of hyper and abnormal phosphorylated Tau protein. Currently, only symptomatic treatments are available. Therefore, the development of curative drugs is a very active research field. Previous work in the laboratory led to the discovery of a family of compounds (MSBD) which lead-compounds are active on both pathologies of the Alzheimer’s disease. A drug candidate, AZP2006, emerged from that research and is currently in phase 1 clinical trials. Investigations on the identification of the biological target of AZP2006 led to p97/VCP protein, a target that has attracted considerable attention over the last few years for the treatment of neurodegenerative diseases (NDD).This PhD thesis deals with three main aspects:1) Study of the interactions between p97/VCP and developed compounds. STD-NMR studies have confirmed the interaction between AZP2006 and p97/VCP, though these preliminary results have to be confirmed by complementary techniques. AZP2006-based chemical probes were designed and synthesized to develop a FRET-based binding assay in order to get a more quantitative characterization of the binding.2) Development of new p97/VCP ligands. Based on previous ligands developed in the laboratory, a pharmacophore model was built. Subsequent, virtual screening and de novo design led to the identification of several chemical structures. Four families were synthesized and tested in vitro showing a good effect on Aβ peptides secretion and APP metabolism. These compounds are being tested on Tau hyperphosphorylation. The binding to p97/VCP was confirmed by STD-NMR.3) Development of multi target compounds acting on both the two pathology of Alzheimer disease and acetylcholinesterase (AChE). Activities of these compounds were validated in vitro (inhibition of AChE, Aβ peptides secretion, APP metabolism and Tau). In vivo, one of the compounds increased cognitive performance in two mice transgenic models.The results obtained during this PhD confirmed the therapeutic potential of p97/VCP in NDD and proposed new structures for their treatment
Berthommier, Frédéric. "Intégration neuronale dans le système auditif : modélisation de réseaux neuronaux temporo-dépendants". Phd thesis, Université Joseph Fourier (Grenoble), 1992. http://tel.archives-ouvertes.fr/tel-00342101.
Texto completoBerthommier, Frédéric. "Intégration neuronale dans le système auditif : modélisation de réseaux neuronaux temporo-dépendants". Phd thesis, Grenoble 1, 1992. https://theses.hal.science/tel-00342101.
Texto completoLenuzza, Natacha. "Modélisation de la réplications des Prions : Implication de la dépendance en taille des agrégats de PrP et de l'hétérogénéité des populations cellulaires". Phd thesis, Ecole Centrale Paris, 2009. http://tel.archives-ouvertes.fr/tel-00453321.
Texto completoSanches, Maria Clara Pires. "Language impairments in neurodegenerative diseases : function, dysfunction and modulation with transcranial stimulation". Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS669.
Texto completoLanguage is one of the most defining features of human beings and for centuries researchers have been interested on the functional organization of language and which neural substrates subtend its normal functioning. A breakdown of mechanisms subtending normal language abilities characterizes different neurodegenerative conditions, which have become models to study the neural basis and mechanisms of language processing. In the absence of effective treatments for language deficits in different neurodegenerative diseases, non-invasive brain stimulation approaches have been gaining momentum. Transcranial Direct Current Stimulation (tDCS) modulates neural activity via the induction of weak electrical intracranial currents, showing benefits in post-stroke and neurodegenerative aphasic patients. In this context, the studies included in this thesis analyzed neurodegenerative lesion models to characterize the behavioral mechanisms of word access and processing, address their impact on language abilities and explore the modulation of language impairment by means of tDCS to define its therapeutic value. The manuscript is divided in 4 chapters organized along three main axes: (1) fundamental research on language (2) clinical research on language breakdown and therapies and (3) impact of individual factors on the variability of the response to such therapies, an Introduction chapter and a General Discussion chapter
Amendola, Julien. "Développement postnatal d'un modèle murin de sclérose latérale amyotrophique : Acquisitions sensori-motrices, fonctionnement des réseaux lombaires et caractérisation des propriétés électriques et morphologiques des motoneurones". Phd thesis, Université de la Méditerranée - Aix-Marseille II, 2008. http://tel.archives-ouvertes.fr/tel-00537888.
Texto completoPan, Teng. "Brain on a chip : to reconstruct multi-nodal neuronal networks in vitro for neurodegenerative disease modelling". Electronic Thesis or Diss., Sorbonne université, 2022. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2022SORUS261.pdf.
Texto completoOrgan-on-a-chip (OoC) is a microfluidic-based miniaturized system that enables to mimic dynamics, functions, physiological and pathological responses of mini-organs in a controlled microenvironment. The brain is a major organ for studying neurodegenerative diseases, and the pattern of NDD propagation in the brain remains unclear. Thus, reconstructing neural networks on a chip could provide a platform for understanding the spreading mechanisms of these diseases. Building neural networks in such miniature systems require addressing the neural network's unidirectionality and the efficiency of the connections between the nodes. In my PhD thesis, I first showed in vitro construction of a unidirectional cortico-striatal neural network using in-mold patterning technics. Then I verified the neural network's connectivity and functionality by calcium imaging immunofluorescence staining. Further, multi-node neural networks were constructed as well. In order to model the propagation mechanisms of neurodegenerative diseases. I used a-synuclein to infect neural networks and observed phosphorylated synuclein in the neural networks. In addition to this, I showed two new methods of fabricating chips to improve the survival of neurons in the chips. Overall, neural networks on a chip could offer more possibilities for studying neurodegenerative diseases
Banus, Cobo Jaume. "Coeur & Cerveau. Lien entre les pathologies cardiovasculaires et la neurodégénérescence par une approche combinée biophysique et statistique". Thesis, Université Côte d'Azur, 2021. http://www.theses.fr/2021COAZ4030.
Texto completoClinical studies have identified several cardiovascular risk factors associated to dementia and cardiac pathologies, but their pathological interaction remains poorly understood. Classically, the investigation of the heart-brain relationship is mostly carried out through statistical analysis exploring the association between cardiac indicators and cognitive biomarkers. This kind of investigations are usually performed in large-scale epidemiological datasets, for which joint measurements of both brain and heart are available. For this reason, most of these analyses are performed on cohorts representing the general population. Therefore, the generalisation of these findings to dementia studies is generally difficult, since extensive assessments of cardiac and cardiovascular function in currently available dementia dataset is usually lacking. Another limiting factor of current studies is the limited interpretability of the complex pathophysiological relations between heart and brain allowed by standard correlation analyses. Improving our understanding of the implications of cardiovascular function in dementia ultimately requires the development of more refined mechanistic models of cardiac physiology, as well as the development of novel approaches allowing to integrate these models with image-based brain biomarkers. To address these challenges, in this thesis we developed new computational tools based on the integration of mechanistic models within a statistical learning framework. First, we studied the association between non-observable physiological indicators, such as cardiac contractility, and brain-derived imaging features. To this end, the parameter-space of a mechanistic model of the cardiac function was constrained during the personalisation stage based on the relationships between the parameters of the cardiac model and brain information. This allows to tackle the ill-posedness of the inverse problem associated to model personalisation, and obtain patient-specific solutions that are comparable population-wise.Second, we developed a probabilistic imputation model that allows to impute missing cardiac information in datasets with limited data. The imputation leverages on the cardiac-brain dynamics learned in a large-scale population analysis, and uses this knowledge to obtain plausible solutions in datasets with partial data. The generative nature of the approach allows to simulate the evolution of cardiac model parameters as brain features change. The framework is based on a conditional variational autoencoder (CVAE) combined with Gaussian process (GP) regression. Third, we analysed the potential role of cardiac model parameters as early biomarkers for dementia, which could help to identify individuals at risk. To this end, we imputed missing cardiac information in an Alzheimer's disease (AD) longitudinal cohort. Next, via disease progression modelling we estimated the disease stage for each individual based on the evolution of biomarkers. This allowed to obtain a model of the disease evolution, to analyse the role of cardiac function in AD, and to identify cardiac model parameters as potential early-stage biomarkers of dementia. These results demonstrate the importance of the developed tools by providing clinically plausible associations between cardiac model parameters and brain imaging features in an epidemiological dataset, as well as highlighting insights about the physiological relationship between cardiac function and dementia biomarkers. The obtained results open new research directions, such as the use of more complex mechanistic models that allow to better characterise the heart-brain relationship, or the use of biophysical cardiac models to derive in-silico biomarkers for identifying individuals at risk of dementia in clinical routine, and/or for their inclusion in neuroprotective trials
Louis, Maxime. "Méthodes numériques et statistiques pour l'analyse de trajectoire dans un cadre de géométrie Riemannienne". Electronic Thesis or Diss., Sorbonne université, 2019. http://www.theses.fr/2019SORUS570.
Texto completoThis PhD proposes new Riemannian geometry tools for the analysis of longitudinal observations of neuro-degenerative subjects. First, we propose a numerical scheme to compute the parallel transport along geodesics. This scheme is efficient as long as the co-metric can be computed efficiently. Then, we tackle the issue of Riemannian manifold learning. We provide some minimal theoretical sanity checks to illustrate that the procedure of Riemannian metric estimation can be relevant. Then, we propose to learn a Riemannian manifold so as to model subject's progressions as geodesics on this manifold. This allows fast inference, extrapolation and classification of the subjects
Lévy, Elise. "Maladies neurodégénératives et stress oxydant". Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASB028.
Texto completoAlzheimer's disease and prion diseases are incurable neurodegenerative diseases associated with the transconformation of a polypeptide: the Aß peptide and the prion protein (PrP) respectively. These misfolded polypeptides then form different aggregates in the brain, leading to neuronal death. In a healthy individual, PrP has a neuroprotective function, but in patients suffering from Alzheimer or prion diseases, the toxicity of some pathological aggregates is mediated by this protein. Moreover, both pathologies are associated with an early chronic oxidative stress, that is toxic. It can promote and be promoted by protein aggregation, without the aggregates involved in this vicious circle being precisely identified.To study oxidative stress in these diseases, I developed innovative cellular models to monitor oxidation markers in real time, and bioinformatic tools to analyze the results. My work shows that the unique expression of the healthy form of Aß or PrP protects cells from an exogenous oxidant. However, the addition to the culture medium of the same cells of recombinant Aß and PrP promotes the appearance of oxidative stress, only for cells expressing normal PrP. This effect is visible for A in the form of amyloid fibrils, and for PrP in the form of monomer, oligomers and potentially amyloid fibrils. This work thus validates the central role of normal PrP in physiology and pathology. My results could suggest a role of glutathione peroxidases in mediating the protective effect of normal PrP, and an activation of NADPH oxidases via PrP in the presence of pathological aggregates
Sacquin, Antoine. "Approches vaccinales des maladies neurodégénératives : applications aux maladies à prions". Paris 6, 2010. http://www.theses.fr/2010PA066327.
Texto completoPons, Vincent. "Rôle du CSF1R dans les maladies neurodégénératives". Doctoral thesis, Université Laval, 2021. http://hdl.handle.net/20.500.11794/68078.
Texto completoAmar-Aguilar, Corinne. "Radicaux libres, superoxyde dismutase et maladies neurodégénératives". Montpellier 1, 1996. http://www.theses.fr/1996MON11078.
Texto completoSambo, Anne-Véronique. "CDK5 et Pin1 : deux enzymes clés dans la dégénérescence neurofibrillaire de type Alzheimer". Lille 2, 2004. http://www.theses.fr/2004LIL2S022.
Texto completoSimard, Alain. "Le rôle des cellules microgliales dans les maladies neurodégénératives". Thesis, Université Laval, 2006. http://www.theses.ulaval.ca/2006/23740/23740.pdf.
Texto completoDecressac, Mickaël. "Potentiel thérapeutique du neuropeptide Y dans les maladies neurodégénératives". Poitiers, 2009. http://theses.edel.univ-poitiers.fr/theses/2009/Decressac-Mickael/2009-Decressac-Mickael-These.pdf.
Texto completoResearch of therapies aiming at preventing the loss of neural cells or inducing their replacement is currently a crucial issue in the field of neurosciences. During my thesis, I was wondering whether the neuropeptide Y (NPY) might have a therapeutic potential for neurodegenerative diseases such as Parkinson’s and Huntington’s disease. Recently, NPY has shown novel proprieties, including its capacity to stimulate the proliferation of neural stem cells and to protect neurons against drug-induced toxicity or in other pathological conditions. In addition, variations of NPY observed in different pathological circumstances tend to believe that this peptide may act as a factor promoting endogenous repair processes in the adult brain. We demonstrated that intracerebroventricular injection of NPY stimulates neurogenesis both in the subventricular zone (SVZ) and the dentate gyrus of the hippocampus. As we observed a migration of newborn SVZ-derived cells towards the striatum and their subsequent differentiation into striatal mature neurons, we then investigated the potential therapeutic interest of NPY in an animal model of Huntington’s disease, where massive loss of striatal neurons occurs. In addition, considering the variations of NPY expression in Parkinson’s and Huntington’s disease patients, we seek to determine whether there is a correlation between serum concentrations of NPY and the grade of the disease, and thus evaluate whether NPY could be a biomarker of these diseases’ progression. Finally, we studied two different therapeutic strategies for Parkinson’s disease. We demonstrated that NPY act as a neuroprotective factor for dopaminergic neurons both in vitro and in an animal model of Parkinson’s disease. In parallel, we reported that transplantation of embryonic midbrain neurons in the substantia nigra leads to a reconstruction of the nigrostriatal pathway and to a functional improvement in an animal model of Parkinson’s disease. Our results open new therapeutic perspectives in the treatment of neurodegerative disorders. Adult brain appears to be permissive to axonal regrowth after lesion, and it seems that it would also be able to respond to neurodegenereation by triggering endogenous
Branchi, Igor. "La souris de laboratoire : modèle d'étude chez l'animal des risques neurotoxiques et des maladies neurodégénératives chez l'humain". Orléans, 2001. http://www.theses.fr/2001ORLE2011.
Texto completoSt-Amour, Isabelle. "Effet des IGIV dans des modèles murins de maladies neurodégénératives". Thesis, Université Laval, 2014. http://www.theses.ulaval.ca/2014/30473/30473.pdf.
Texto completoIn the search of therapeutic solutions to neurodegenerative diseases, active and passive immunization strategies have been proposed for the clearance of protein aggregates. Intravenous immunoglobulin (IVIg) is a pharmaceutical preparation of over 98% immunoglobulin G prepared from the plasma of thousands of healthy donors. Since natural autoantibodies against pathological proteins have been identified in IVIg, it has been proposed as an alternative to immunotherapy and clinical trials in Alzheimer’s disease (AD) patients are underway. The aim of my PhD project was to evaluate the efficacy, analyze the mechanisms of action of IVIg in animal models of AD and Parkinson’s disease (PD), and identify potential targets for the development of pharmacological alternatives. The bioavailability of IVIg and its ability to reach therapeutic targets in the brain are unknown. In the first part of the project, we quantified the passage of IVIg through the blood-brain barrier (BBB). Our results provide quantitative evidence of BBB transport and brain bioavailability of IVIg in the absence of permeabilization and in sufficient amount to interact with therapeutic targets. In a triple transgenic mouse model of AD (3xTg-AD) that reproduces amyloid and tau pathologies, IVIg injections have improved the cognitive performance and reduced anxiety-like behaviors of treated mice. Despite limited effects on tau pathology, IVIg modulated the central (IL-5/IL-10 ratio) and peripheral (CX3CR1 + and T cells), and reduced the ratio of soluble Aβ42/Aβ40 (-22%) and the concentration of 56 kDa oligomers of Aß (Aß*56) by over 60%. This effect of IVIg on cognition, immunity and Aß pathology suggests that Aβ oligomers, effector T cells and the fractalkine pathway are potential pharmacological targets of IVIg in AD. Finally, we studied the effect of an IVIg treatment in a mouse model of PD. In this model of MPTP intoxication, our results did not demonstrate neurorestorative effects of IVIg on the nigrostriatal system and even suggested adverse effects of IVIg on the dopaminergic system. These preclinical data highlighted the importance of proceeding cautiously in the initiation of clinical trials with IVIg to treat PD patients.
Miled, Samia. "La levure S. Pombe : un modèle d'étude des maladies neurodégénératives". Paris 7, 2009. http://www.theses.fr/2009PA077174.
Texto completoThe mechanisms of maintaining genetic stability in quiescence/GO phase, as differentiate neurons, are little known. The large number of neurodegenerative diseases caused by mutations in DNA repair genes suggests that the genome of post-mitotic neurons is at high risk. The power of yeast genetics and the strong conservation of basic cellular processes between yeast and higher organisms have made the yeast as a model organism for basic research and drug development. During my thesis, I have tried to show that the yeast S. Pombe is a simple and relevant model for understanding the mechanisms of genetic stability in the quiescent cells. To achieve this goal, I showed the importance of a gene conserved during evolution, called tdpl, which encodes a tyrosyl-DNA phosphodiesterase, in DNA repair and maintaining the viability of quiescent cells. I have also shown that the lethality of tdpl mutant in GO is suppressed when the mitochondrial respiration is slowed and in the presence of antioxidant molecules such as vitamins. Thus, with a respiratory metabolism and mitochondrial chromosome of the same size as that of human, the yeast S. Pombe, appears to be a good model for studying the mechanisms of DNA repair in GO. My second aim was to evaluate the involvement of the major pathways of DNA repair in quiescent state. This approach allowed me to determine the hierarchy of DNA repair pathways and provide a better understanding of the DNA damage types occurring in quiescence. Thus, showing that thé yeast, which hâve been recognized as effective model to study the carcinogenesis process, can behave like neurons. The development of such a model should not only serve as an original research tool for SCAN1 disease, caused by a tdpl mutation, but also open new exploration areas for other neurodegenerative diseases like AOA1
Mazère, Joachim. "Interactions acétylcholine-dopamine dans les maladies neurodégénératives : approche d’imagerie moléculaire". Thesis, Bordeaux 2, 2011. http://www.theses.fr/2011BOR21873/document.
Texto completoThe question of how acetylcholine (ACh) and dopamine (DA) could be involved together in the pathophysiology of some neurodegenerative disorders is essential, particularly in dementia with Lewy bodies (DLB). The present study aims at assessing an in vivo molecular imaging method of both ACh and DA brain systems using single photon emission computed tomography. In the first part of the present study, a method based on pharmacokinetic analysis making it possible to quantify ACh neurons in vivo, using [123I]-IBVM, a specific radioligand of vesicular acetylcholine transporter, was developed and validated in healthy subjects and Alzheimer’s disease patients. Then, we showed the ability of our method to demonstrate a differential alteration of ACh pathways in Progressive Supranuclear Palsy and Multiple System Atrophy patients. In the last part of this study, we imaged for the first time both ACh and DA systems in DLB patients, using not only [123I]-IBVM, but also [123I]-FP-CIT, a specific radioligand of dopamine transporter. Concomitantly, a behavioral exploration of hallucinations, fluctuating cognition and disturbances of circadian rhythms was achieved in these patients, as well as a neuropsychological examination. This study is currently in progress. The first results show consistent links between imaging and clinical data
Sauzéat, Lucie. "Vieillissement et maladies neurodégénératives : nouvelles contraintes apportées par la métallomique". Thesis, Lyon, 2018. http://www.theses.fr/2018LYSEN005/document.
Texto completoCharacterized by the progressive and irreversible decline of vital biological functions, ageing is a complex biological process that often comes with neurodegenerative disorders. In 2050, more than 1.5 billion elderly are expected in the world. Improve the quality of life of these ageing people is therefore a major challenge for our society. Still poorly known, the progressive degradation of the metallome is asscociated with ageing and neurodegenerative diseases development and is probably one of their causes. The objective of this study is to better characterize the metallome evolution in two animal models over time i.e. the mouse and the worm as well as in human affected by amyotrophic lateral sclerosis (ALS). To do this, we analyzed twenty trace and major elements as well as the isotopic compositions of copper (δ65Cu) and zinc (δ66Zn) of mouse organs, different strains of nematodes, and human cerebrospinal fluid (CSFs).The analysis of mouse organs shows that important chemical and isotopic changes develop in the body over time, each organ having its own elemental and isotopic signature. For example, we observe an increase of the Cu concentration in the brain associated with a decrease of the δ65Cu in the liver over time. Based on the analysis of metabolomic parameters and the use of isotopic mixings, we show that these variations may be explained by major physiological and metabolic dysfunctions, such as the deregulation of hepatic fluxes and/or the degradation of the blood-brain barrier with age. This suggests that the temporal analysis of the metallome could be used as a potential marker of the biological age.The analysis of nematodes revealed that long-lived animals differ from short-lived nematodes by an early-age decrease in their Cu isotopic composition and Cu concentration. The temporal monitoring of these biomarkers could therefore be used to detect premature ageing conditions.Finally, the analysis of CSFs of patients with amyotrophic lateral sclerosis (ALS), a severe neurodegenerative disease for which there is currently no reliable biomarker or treatment, shows that ALS patients have a higher δ65Cu compared to healthy subjects and Alzheimer’s disease patients. This feature, offering new perspectives to identify ALS-specific biomarkers, may be explained by the formation of toxic protein aggregates in the brain
Hoy, Aline. "La Myéloperoxydase : marqueur et cible pharmacologique potentielle dans les pathologies cardiovasculaires et neurodégénératives". Nancy 1, 2002. http://www.theses.fr/2002NAN12505.
Texto completoGélinas, Sylvie. "Analyse structurale des neurofilaments et leur implication dans les maladies neurodégénératives". Thèse, Université du Québec à Trois-Rivières, 1998. http://depot-e.uqtr.ca/3544/1/000651935.pdf.
Texto completoVallée, Alexandre. "Molecular thermodynamic aspects of dissipative structures in oncology, inflammatory and degenerative processes of Central Nervous System diseases". Thesis, Poitiers, 2017. http://www.theses.fr/2017POIT1409.
Texto completoEnergy metabolism is the primary determinant of cellular viability. Diseases are the sites of numerous metabolic and energetic production abnormalities. Indeed, the altered cells are derived from exergonic processes and emit heat that flows to the surrounding environment. Many irreversible processes can occur through changing the rate of entropy production. This rate represents a thermodynamic quantity that measures these irreversible processes. Entropy rate is increased by several metabolic and thermodynamics abnormalities in brain tumors, inflammatory processes and neurodegenerative diseases. The research works of this thesis have demonstrated and highlighted the existence of a crosstalk between canonical WNT/beta-catenin pathway and PPAR gamma which plays a major role in the reprogramming of cellular energy metabolism between oxidative phosphorylation, aerobic glycolysis and anaerobic glycolysis, of which the equilibrium point of crosstalk between these molecular pathways varies according to tumor, inflammatory and neurodegenerative diseases. These diseases are dissipative structures, that exchange energy or matter with their environment. They are open systems, far-from the thermodynamic equilibrium that operate under non-linear regime evolving to non-stationary states. Far-from-equilibrium thermodynamics are notions driven by circadian rhythms. Indeed, circadian rhythms directly participate in regulating the crosstalk of the studied molecular pathways. This crosstalk represents an innovative therapeutic target, and molecular data usable for molecular imaging in both positive and differential diagnosis of these diseases
Fillebeen, Carine. "La lactoferrine cérébrale : origines et mécanismes d'accumulation au cours des maladies neurodégénératives". Lille 1, 1999. https://pepite-depot.univ-lille.fr/LIBRE/Th_Num/1999/50376-1999-171.pdf.
Texto completoIskandar, Samy. "Développement de formes vectorisables innovantes dans le cadre de maladies liées à l'âge". Thesis, Aix-Marseille, 2019. http://theses.univ-amu.fr.lama.univ-amu.fr/191211_ISKANDAR_942qv952dpkqb571ugya506omy_TH.pdf.
Texto completoAlzheimer's disease is a degenerative brain disease where abnormal chemicals accumulate causing progressive deterioration of memory and intellectual ability. It is a neurodegenerative disease that causes lesions in the brain. Irreversible lesions lead to a decline in cognitive functions, which serve to process information, and behavioral as the disease progresses. Loss of immediate memory, and then older memories, changes in judgment and reasoning, changes in mood and behavior are the main manifestations.Contrary to popular belief, Alzheimer's disease is not related to the normal aging of the brain. Today, the cost of the disease in Europe is estimated at 160 million euros/year, despite that, there is no effective symptomatic treatment.New non-drug approaches should be explored to slow the progression of the disease. Research in the field of the "Drug Delivery System" reveals increasingly promising systems. Addressing molecules of therapeutic interest to a target tissue is a major challenge in Drug Delivery. New targeting technologies have emerged. The search for vectors having a sufficiently long life in the body to reach the target area has already been put in place. This work is a modest step in the exploration of nanovectorized herbal medicine for the treatment of Alzheimer's disease
Chrysostome, Virginie. "Analyse intermédiaire de l'étude MSA-Aquitaine : prévalence, facteurs de risque environnementaux et histoire naturelle de l'atrophie multisystématisée". Bordeaux 2, 2000. http://www.theses.fr/2000BOR23080.
Texto completoAttarian, Shahram. "La Sclérose latérale amyotrophique : investigation micro-électromyographique longitudinale des atteintes spinales et corticales". Aix-Marseille 2, 2007. http://www.theses.fr/2007AIX20685.
Texto completoComte, Caroline. "Caractérisation d’ARN artificiels importables dans les mitochondries humaines à des fins thérapeutiques". Strasbourg, 2010. https://publication-theses.unistra.fr/public/theses_doctorat/2010/COMTE_Caroline_2010.pdf.
Texto completoMitochondrial DNA mutations, important cause of incurable human neuromuscular diseases, are mostly heteroplasmic: mutated mtDNA is present in cells simultaneously with wild-type genomes, the pathogenic threshold being generally > 70% of mutant mtDNA. We studied if heteroplasmy level could be decreased by RNAs complementary to mutant mtDNA regions. To target specifically designed oligoribonucleotides into the organelle, mitochondrial import of RNA was exploited, the pathway delivering nucleic acids into mitochondria in vivo. Using mitochondrially targeted RNAs as mitochondrial vectors we demonstrated, in cultured transmitochondrial cybrid cells, that RNAs complementary to the mutant mtDNA region can specifically reduce the proportion of mtDNA bearing a large deletion associated with the Kearns Sayre Syndrome. These findings may be relevant to developing of a new tool for therapy of mtDNA associated diseases
Thomas, Sophie. "PCP4, trisomie 21 et maladies neurodégénératives : construction et étude de modèles murins". Paris 5, 2005. http://www.theses.fr/2005PA05N16S.
Texto completoPCP4 (PEP-19) belongs to a family of Iq motif proteins involved in calcium transduction signals. It binds calmodulin and regulates CamKII and nNOS wich are involved in neuronal plasticity and wich may also mediate the transduction of apoptotic signal. The gene is localized on HSA21 and is in 3 copies in Down syndrome (DS) patients. To determine whether PCP4 may be involved in some DS phenotypic features, we analysed its expression pattern during mouse development and in the adult brain. PC expression pattern suggests that its overexpression may be involved in some of the DS features such as abnormalities in neuronal differentiation in cluding synaptogenesis and migration. We thus constructed a mouse model of PCP4 overexpression using the ES cells transgenesis method. The transgenicline is currently under study. PCP4 expression in the aging brain has been shown not to vary systematically during normal aging suggesting that PCP4 modulations in human neuropathologies are induced by genes involved in these diseases. Moreover, microarrays analysis suggests that PCP4 modulation is associated with other genes involved in neurotransmission
Tomassoli, Isabelle. "Synthèse et évaluation de nouveaux dérivés quinoléiques impliqués dans les maladies neurodégénératives". Besançon, 2010. http://www.theses.fr/2010BESA0015.
Texto completoNeurodegenerative's diseases and especially Alzheimer's disease are the most common forms of senile dementia. From the neuropathological point of view several factors could be at their origin. The oxidative stress and the deficit cholinergic are main causes of this disease. During this thesis we were interested in the synthesis and the biological assessment of new compounds as antioxydant and cholinesterase inhibitors. These compounds contain a quinoline nucleus. The choice of this heterocycle derives from its biological properties in very varied fields and also from the studies made previously in our laboratory. Work comprises four sections connected with four series of quinolines derivates : 1,2-dihydroquinoline-3carboxamides, 1,2-dihydroquinoline-3carbohydrazides, Dihydropyrimidoquinolines, Pyrazoloquinolines. Forty new compounds have been synthetized. Dihydropyrimidoquinolines were prepared by application of the Biginelli reaction. This " one-pot " and multi-compounds reaction leads easily and fastly to quinolines nucleus. The other series were prepared in a multi-step strategy from isatoic anhydride and its derivate. Biological assessments was then estimated. 1,2-dihydroquinoline-3carboxamides and 1,2-dihydroquinoline-3carbohydrazides were tested as antioxydant, metal chelators and cholinesterase inhibitor. We used for these compounds an approach pharmacophore based design. Dihydropyrimidoquinolines and Pyrazoloquinolines were tested as cholinesterase inhibitors. The docking of every active compounds have been done and shown interactions between compounds and the enzyme
Coowar, Djalil. "Cellules souches et maladies neurodégénératives : Conception et synthèse d'inducteurs de différenciation cellulaire". Université Louis Pasteur (Strasbourg) (1971-2008), 2003. http://www.theses.fr/2003STR13211.
Texto completoIn a search for inducers of neuronal differentiation to treat neurodegenerative diseases such as Alzheimer's disease or Amyotrophic Lateral Sclerosis, a series of indole fatty alcohols (IFA) were synthesised. These molecules combine a long chain w-alkanol with an antioxidant core. Melatonin being a well-known antioxidant, the indole ring bearing or not methoxy groups on the benzene moiety was chosen. A Wittig reaction between indole-3-carboxaldehydes and long chain phosphorous ylides was the key step in the preparation of these IFAs. These compounds were then investigated for their free radical scavenger property and their effect on the differentiation of neural stem cells-derived neurospheres. The presence of the hydroxyl group was essential to increase the antioxidant potency of IFAs compared to melatonin. Additionally, we showed that 5MIFA18 promotes the differentiation of neural stem cells-derived neurospheres into neurons at a concentration of 10 nM. Our results suggest that this effect is likely to exert on neuronal progenitors rather than on uncommitted precursors, with 5MIFA18 promoting their differentiation. This finding supports the notion that this molecule acts as a neurotrophic factor. Analysis of the expression of the Notch pathway genes in neurospheres treated during differentiation with 5MIFA18 revealed a significant decrease in the transcription of Notch 4 gene receptor. We hence develop a new synthesis for C-5 substituted indole fatty alcohols using a Suzuki reaction
Munch, Maxime. "Synthèse et étude de fluorophores organiques pour la détection de maladies neurodégénératives". Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAF031.
Texto completoThis research concerns the synthesis and photophysical studies of organic fluorescent probes applied to the detection of two Alzheimer’s disease biomarkers: the protein kinase C and fibrils of amyloid Aβ42 peptides. PKC detection is achieved by dyads composed of boradiazaindacene dye (BODIPY) covalently linked to an inhibitor of this enzyme. These compounds afforded by a multistep synthesis display high molar absorption coefficients and quantum yields in solution. These probes were then used in flow cytometry by Amoneta Diagnostics to detect PKC on the surface of red blood cells in order to asses the potential of these molecules for the diagnostic of Alzheimer’s disease by blood test. Two series of fluorophores from the 2-(2’-hydroxyphenyl)-benzazole family have been studied for the detection of amyloid fibrils. These molecules display an excited state intramolecular proton transfer (ESIPT) phenomenon which confer them remarkable optical properties such as important Stokes shifts and dual emission. Finally, an in vitro detection test has been developed. Interactions between these dyes and amyloid fibrils has been observed, allowing the detection of these peptides in solution
Palaniyandi, Ravanan. "Modulation de l'inflammation dans le tissus adipeux : implication potentielle dans la neurodégénérescence induite chimiquement". La Réunion, 2007. http://elgebar.univ-reunion.fr/login?url=http://thesesenligne.univ.run/07_05_Palaniyandi.pdf.
Texto completoObesity is a significant risk factor for several diseases including the insulin resistance syndrome. White fat tissue (WAT) is considered as an endocrine organ with the capacity to produce adipokines. The aim of this work was to study the effects of a neurotoxic agent on WAT’s inflammation and to investigate the effect of an anti-inflammatory drug on WAT. We used, Trimethyltin (TMT), a neurotoxin known to induce an inflammatory response in the CNS and Palmitoylethanolamide (PEA), an anti-inflammatory drug. TMT induced the production of pro-inflammatory cytokines in WAT both in vitro and in vivo, demonstrating that cell types from the WAT are capable of responding to a neurotoxin. In addition, associated with TNF- level increase in the serum, the severity of hippocampal damage and activation of glial cells were more pronounced in agouti than in control mice. We also tested the effect of PEA on adipocytes and the results showed that this molecule inhibits TNF- secretion induced by Lipopolysaccharide both in vitro and in vivo, suggesting that PEA could be explored for therapeutic purposes as an anti-inflammatory drug for obesity associated diseases
Dequen, Florence. "Filaments intermédiaires neuronaux et maladies neurodégénératives : caractérisation de nouveaux modèles de souris transgéniques". Thesis, Université Laval, 2009. http://www.theses.ulaval.ca/2009/26415/26415.pdf.
Texto completoLafon, Pierre-André. "Impact des pesticides sur l'agrégation des amyloïdes dans différents modèles de maladies neurodégénératives". Thesis, Montpellier, 2019. http://www.theses.fr/2019MONTT005.
Texto completoContamination of the drinking water and agricultural lands by the use of pesticides entering into the food chain is a major environmental and health problem. Epidemiological studies have shown a link between pesticide exposure and Parkinson's disease, but few studies are available on other neurodegenerative disorders. Our hypothesis is that pesticides may be triggering or aggravating factors common to neurodegenerative diseases.In the laboratory, we identified by a screening on the prion protein, PrP, a compound named A6 described for its herbicidal properties. A6 is a derivative of α-terthienyl, a natural molecule extracted from marigolds. A6 compound has the ability to promote oligomeric forms of the prion protein on a prion-infected cell line. My research project aimed to study the effects of the bioherbicide A6 on prion aggregation and propagation in vivo. Mice infected with prions were treated with different doses of this molecule (5, 10 and 20 mg/kg). At the dose of 5 mg/kg, A6 compound decreases the survival time of animals with an increase of the amyloid load. While at the higher doses, A6 treatment increases survival of mice with a decreased amyloid burden. Using a rapid centrifugation assay (RCA), we have shown that low concentrations of A6 promote soluble SDS-resistant oligomers of PrPSc (rSDS-PrPSc), while higher concentrations favour insoluble forms. Brain analysis shows that only mice treated with 10 and 20 mg/kg of A6 exhibit dimeric forms of rSDS-PrPSc. This study shows a dual effect of A6 compound: at low doses, it strenghtens the pathology probably via soluble oligomeric forms favouring the replication of prions. At higher doses, A6 compound would trap part of the infectivity of prions as SDS resistant amorphous aggregates, blocking prion replication, and thus having a “protective” effectA search for structural analogs of A6 compound allowed the identification of a class of commercial antifungals: anilinopyrimidines. This family is composed of 3 molecules: cyprodinil, mepanipyrim and pyrimethanil, used to fight against fungi responsible for the gray mold of fruits. Analysis of many reports have revealed that we are chronically exposed to residues of anilinopyrimidines. In this second study, we evaluated the impact of the 3 fungicides in several models of Alzheimer’s disease (AD) and their consequences on pathological markers. Ex vivo incubation studies associated to kinetics of fibril formation of Aβ1-42 peptides have shown that these compounds interact directly with Aβ peptides and accelerate its kinetics of aggregation. To determine their effects in vivo, we chronically exposed J20 mice to a cocktail of the 3 fungicides through drinking water. Mice were treated with 0.1 μg/L (0.44 nM) of each compound, corresponding to the maximal concentration allowed in the tap water. After 9 months of treatment, analysis of J20 mice showed an increase in the number and surface of plaques in the hippocampus and cortex. To determine the moment when the pro-aggregative effect occurs, a longitudinal study of appearance of aggregates at 3, 6 and 9 months by 2-photon microscopy was done. Our results showed that amyloid plaques increase between 6 and 9 months, and exacerbate vascular amyloid aggregates. Anilinopyrimidines modified the production and clearance of Aβ peptides by increasing BACE1 expression and by decreasing neprilysin expression. Our researches show a role of fungicides in the aggravation of AD
Fenyi, Alexis. "Typage moléculaire des maladies neurodégénératives dues à l’agrégation de la protéine alpha synucléine". Thesis, Université Paris-Saclay (ComUE), 2019. http://www.theses.fr/2019SACLS053.
Texto completoThe aggregation of α-synuclein protein has been shown to be associated with Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, called synucleinopathies. Increasing amount of evidences suggest that synucleinopathies are prion diseases. Some aspects are missing for α-synuclein to be recognized as a prion, such as the existence of strains associated to synucleinopathies. During my thesis I set up a reliable method to amplify α-synuclein-rich deposits from patients tissues. I validated the method using all synucleinopathies tissues. This should allow the identification of α-synuclein strain related to each synucleinopathy. In addition, I also documented cleaning procedures for materials soiled with various amyloid fibers, in order to reduce the risk of contamination. Finally, I was associated to a study that shows the propagation abilities of different α-synuclein assemblies in a neuronal network mimicking human cortico-cortical connections. These results open the way to structural and functional studies of the amplified deposits
Cornille, Emilie. "L'hypométabolisme énergétique, une cible pour le traitement des maladies neurodégénératives : étude de faisabilité". Aix-Marseille 2, 2009. http://www.theses.fr/2009AIX20730.
Texto completoAll the neurodegenerative diseases are to some extent associated with metabolic dysfunctions, characterized by impairment of the glycolytic pathway, the main cerebral energetic source. However, the brain has the ability to use an alternative carbon source for energy production, the lipids. The process, known as fatty acid -oxidation, involves an oxidoreductase superfamily, which uses substrates made of fatty acid linked to Coenzyme A (CoA) via a thioester bond. These enzymes include numerous isoforms, in relation to the highly structural variability of fatty acids. The end products of the process are the ketone bodies -hydroxybutyrate and acetoacetate. When administered to rat or mice, or used in in vitro studies, ketone bodies exert a neuroprotective effect in the context of many diseases. However, as far as chronic diseases are concerned, a long-term administration of these compounds has adverse effects not yet well assessed. Therefore a better strategy would be to regulate the fatty acid -oxidation pathway i. E. To enhance it, however only when necessary. We explored this possibility in the MPTP mouse model of Parkinson’s disease, using pantethine, the pro-vitamin B5, a thiol widely spread in the living world. The choice of this compound is dictated by the fact that its reduced form, pantetheine, constitutes the active moiety of CoA. Therefore pantethine/pantetheine is the necessary cofactor for lipid metabolism, including fatty acid -oxidation. We determined 3--hydroxyacyl-CoA dehydrogenase (HAD) activity, which catalyses 3--hydroxybutyryl-CoA oxidation, yielding acetoacetyl-CoA. We found that the enzyme was inhibited in MPTP-intoxicated mice. The activity was restored by pantethine treatment, leading to the increase of circulating levels of ketone bodies. We underline that this rise was observed only in MPTP-intoxicated mice, not in healthy ones. The overall result was mitigation of dopaminergic injury in the nigrostriatal area, in such a way to allow normal mouse motility. In fact, protection is likely to be due to a cumulative effect of the treatment: even though pantethine is a small and simple structure, it displays a multifaceted activity. Among other properties, pantethine is anti-inflammatory (by inducing the enhancement of GSH stores and by inhibiting the activation of cell response to pro-inflammatory factors), antioxidant and hypolipidemic. In conclusion, our work illustrated the feasibility of a therapeutic strategy which targets simultaneously several events in the pathogenic cascade leading to Parkinson’s disease, including the restoration of the energy metabolism. Our opinion is that such approach could be applied to other complex diseases. Preliminary studies on Friedreich ataxia and cerebral malaria tend to confirm our hypothesis
Boughali, Hicham. "Monoxyde d'azote et inhibition métabolique : implications neurodégénératives". Paris 5, 1998. http://www.theses.fr/1998PA05P154.
Texto completoKhoyratee, Farad. "Conception d’une plateforme modulable de réseau de neurones biomimétiques pour l’étude des maladies neurodégénératives". Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0351.
Texto completoNeuroscience has been the subject of many studies and has seen new fields of research emerge where technology and biology can be used to find solutions to understand and cure neurological diseases. These illness affect millions of people around the world. The World Health Organization (WHO) predicts a 3 fold increase in the number of patients in the next 30 years.Advances in neuroscience have led to the development of models describing the physiology of neurons and also methods of hardware implementation of these models. Among these methods, neuroprosthesis are devices for restoring certain neuronal functions through communication with the nervous system.This thesis work show that the realization of the biomimetic system was carried out thanks to digital components such as Field Programmable Gate Array (FPGA) which allows to benefit from the flexibility and speed of prototyping of these technologies. The real-time platform of biologically realistic neural networks developed is configurable. It becomes a neuro-computational tool allowing the realization of bio-hybrid experiments for the study of the behavior of the nervous system and more particularly of the neurodegenerative diseases.This work was placed in a larger context. The FPGA digital operator library developed for the platform has been reused for the study of dynamics similar to neural networks such as biochemical network simulation or combinatorial optimization problem solving
Ciancia, Marion. "Rôle des rétinoïdes dans le contrôle du système dopaminergique et les maladies neurodégénératives associées". Thesis, Strasbourg, 2018. http://www.theses.fr/2018STRAJ113.
Texto completoA disturbed dopaminergic signaling in the striatum leads to motor disorders such as Huntington’s (HD) and Parkinson’s (PD) diseases. A decrease of the retinoic acid (RA) signaling is observed in patients presenting disorders of the nogro-striatal pathway as well as in HD and PD models. Our data indicate that RALDH1-synthesized RA that binds the receptor RARβ in the striatum is essential to maintain the nigro-striatal system. A disturbance in this RA signaling leads to a decreased mitochondrial respiration, an increased oxidative stress and an increased apoptosis in the dorso-lateral striatum. This cellular alterations lead to HD-like and PD-like motor disorders A rescue of the striatal RA level or the stimulation of RARβ by a specific agonist prevent this phenotypes. Our work allow us to point at RARβ as a new potential therapeutic target for neurodegenerescences like HD and PD
Quoniam, Nolwenn. "L'apathie dans la maladie d'Alzheimer et la démence fronto-temporale". Paris 5, 2007. http://www.theses.fr/2007PA05H048.
Texto completoThis thesis examined mechanisms of apathy in Alzheimer's disease (AD) and fronto-temporal dementia (FTD). Therefore we included 36 AD, 13 FTD and 29 control subjects. Results showed different profiles of apathy depending on the pathology : among the FTDs, apathy was global, involving all activity fields, whereas among the Ads, apathy was selective, involving only some activity field. Each of these apathy profiles was related to different psycho-affective and behavioural disturbances. The FTDs showed dysexecutive syndrome related with frontal behavioural troubles. On the contrary, ADs showed less important executive and frontal perturbations related to other troubles (depression) that do no exist among the FTDs. Apathy seemed related with organic mechanisms (because evolving with the intensity of the cognitive deficiency) and/or psycho-affective mechanisms (depression, anxiety due to repeated failures)
Rival, Thomas. "Mise en évidence du rôle des transporteurs du glutamate dans la physiologie synaptique et la prévention des neurodégénérescences chez la Drosophile". Aix-Marseille 2, 2005. http://www.theses.fr/2005AIX22043.
Texto completoIn Drosophila, glutamate is the neurotransmitter at neuromuscular junctions (NMJ) and in the central nervous system (CNS). We studied Drosophila homologues of genes coding for re-uptake glutamate transporters (EAAT) and vesicular glutamate transporters (VGLUT). DEAAT1, the only EAAT Drosophila glutamate transporter, is expressed in glial extensions that project in the neuropil. Inactivation of dEAAT1 by RNA interference led to increased duration of muscle potential, behavior deficits, shortened life span, increased sensitivity to oxidative stress and neuropil degeneration. These results demonstrate that dEAAT1 participates to the removal of glutamate at synapses, and prevent glutamate-induced neurotoxicity. We isolated DVGLUT a VGLUT gene. DVGLUT represented the first available marker of central glutamatergic synapses. Surprisingly, DVGLUT positive glutamatergic synapses were found in high abundance in the CNS. This suggests that glutamate is a major neurotransmitter in the Drosophila
Liévens, Jean-Charles. "Etude des conséquences de l'altération du transport du glutamate et de la régulation de l'expression des transporteurs du glutamate au niveau du striatum chez le rat". Aix-Marseille 2, 2000. http://www.theses.fr/2000AIX22001.
Texto completoNieweg, Katja. "Cholesterol biosynthesis in neurons and glial cells". Université Louis Pasteur (Strasbourg) (1971-2008), 2007. https://publication-theses.unistra.fr/public/theses_doctorat/2007/NIEWEG_Katja_2007.pdf.
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