Дисертації з теми "Maladie de Parkinson – Effets du stress"
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Issa, Sabi Abdul-Raouf. "Stress oxydatif et vieillissement neuronal dans des modèles de la maladie de Parkinson chez la drosophile : effets protecteurs des protéines découplantes mitochondriales et de l'autophagie médiée par les chaperonnes." Thesis, Paris 6, 2015. http://www.theses.fr/2015PA066405.
Parkinson's disease (PD) is characterized by progressive motor disorders resulting in dopaminergic neurons degeneration in the substantia nigra. In this pathology, aging is a major predisposing factor. During my thesis, I examined initially, in vivo models used in the laboratory to study the PD in Drosophila, namely the expression of α-synuclein and paraquat. I have contributed to the identification of dopaminergic neurons subpopulation involved in locomotor effects of α-synuclein and highlighting the role of a dopamine D1-like receptor in neurotoxicity of paraquat. I then shown that the activity of dopaminergic neurons accelerated senescence and decreases Drosophila lifespan by contributing significantly to the production of ROS in the brain. Finally, we identified and characterized Drosophila homologous of LAMP-2A protein, involves in autophagy-mediated chaperone (AMC), and demonstrated that the increase in neuronal clearance of cytosolic proteins by the expression human LAMP-2A or its Drosophila homologue has positive effects on the locomotor decline associated with aging and resistance against PD factors, but it does not increase longevity. These results suggest that the CMA is a conserved mechanism in Drosophila and its activation protects against oxidative stress and neuronal aging
Besnault, Pierre. "Impact pathologique du stress chronique dans la maladie de Parkinson : rôle des récepteurs aux glucocorticoïdes dans la régulation des organelles de signalisation immunitaire innée." Electronic Thesis or Diss., Sorbonne université, 2023. http://www.theses.fr/2023SORUS534.
This project focuses on the pathological consequences of chronic stress (CS) and the alteration of signaling mediated by glucocorticoids (GCs) and their receptors (GRs) in Parkinson's disease (PD). Stress stimulates the hypothalamic-pituitary-adrenal (HPA) axis and the secretion of GCs that triggers a large number of physiological responses which are beneficial in the short term. On the other hand, CS disrupts the HPA axis, alters these physiological responses and leads to the development of neuropsychiatric disorders such as depression, a known risk factor for PD. In line with this, evidence suggests that the HPA axis is altered in PD patients together with a central alteration of GC/GR signaling. How could these alterations impact the pathomechanisms and contribute to disease progression? PD is an uncurable neurological disorder of still unknown origin. Sporadic form of the disease represents a very large majority of PD cases, and probably results from complex interactions between genetic and environmental risk factors. Clinically, PD is diagnosed upon identification of motor symptoms resulting from a massive loss of dopaminergic neurons in the substantia nigra. Neurodegeneration is associated with the aggregation of alpha-synuclein (aSyn) that deposits into intraneuronal inclusions known as Lewy bodies and neurites. Associated with neurodegeneration, immune responses orchestrating inflammatory processes are mounted and likely involved in disease progression. In the past years, one of the greatest finding regarding the mechanism of immune cell activation in PD has been the discovery of the structural properties of aSyn assemblies being able to act as true pathogen-associated molecular pattern, and to mediate the activation of supramolecular organizing centers (SMOCs), which are considered as important innate immune signaling platforms. Given that one of the major properties of GR is to regulate inflammatory response in immune cells, we hypothesize that chronic stress-mediated HPA axis and GC/GR signaling alterations could exacerbate inflammatory responses through an overactivation of SMOC-dependent signaling. Our work shows that CS not only alters microglial GC/GR signaling, but also increases neuronal death and microglia-associated inflammatory response in a mouse model of PD. Understanding precisely the link between the alteration of GC/GR signaling and the increase in the inflammatory response by focusing on SMOC-dependent signaling will allow us to better understand the different pathophysiological molecular mechanisms, but also identify new therapeutic targets
Levet, Clémence. "Mild Endoplasmic Reticulum Stress Protects From Cell Death : The Role Of Autophagy." Thesis, Lyon 1, 2012. http://www.theses.fr/2012LYO10209.
The last years have been very successful in identifying mechanisms, which control apoptosis in metazoan. However, the regulation of cell death in specific cell type remains to be determined. An excess of neuron apoptosis can lead to neurodegenerative diseases such as Huntington, Parkinson or Alzheimer diseases. Neurodegeneration is usually associated to Endoplasmic Reticulum stress (ER stress), autophagy or oxidative stress. However, the role of these mechanisms in the regulation of neurodegeneration is not clearly established. To test the role of ER stress in the regulation of neuronal death, we used several models of neurodegeneration in Drosophila and mammals. First, we have shown that the genetic induction of ER stress protected photoreceptors of the Drosophila eye from apoptosis. Then, we have shown that the protective effect of ER stress is conserved in both Drosophila and mouse models of Parkinson disease. In order to characterize the protective effect of ER stress, we have studied the activation of protective mechanisms upon ER stress. We have shown that in the Drosophila retina, ER stress can induce an anti-oxidative response and autophagy. Interestingly, autophagy is only activated in presence of both ER stress and cell death signal. We have focused on the role of autophagy in the protective effect of ER stress. We have shown that the activation of autophagy was required for the protective effect of ER stress. Thus, we have shown that ER stress response is not only involved in the reduction of misfolded protein accumulation, but can also protect neurons form cell death by activating autophagy
Séré, Yves Yacouba. "Effet de la biosynthèse de lipides sur la toxicité de l'α-synucléine, protéine impliquée dans la maladie de Parkinson, chez Saccharomyces cerevisiae". Poitiers, 2010. http://theses.edel.univ-poitiers.fr/theses/2010/Sere-Yves-Yacouba/2010-Sere-Yves-Yacouba-These.pdf.
Parkinson’s disease is a neurodegenerative pathology that has been linked to several genetic mutations of the SNCA gene encoding the pro-oxidant α-synuclein protein. The budding yeast S. Cerevisiae is a valuable model to study cellular and molecular mechanisms of α-synuclein toxicity. Indeed heterologous expression of α-synuclein is toxic to wild type yeast, and recapitulates the main features of damages caused to mammalian neurons including an increase of neutral lipids storage (triglycerides and steryl esters, embedded into lipid droplets). To address the significance of this accumulation, we forced α-synuclein production in a strain unable to synthesize triglycerides and steryl esters. Surprisingly, inability to store neutral lipids rendered cells more tolerant to α-synuclein. Our results indicate that the level of !-synuclein toxicity is correlated to fatty acid synthase activity and intracellular redox state
Rahbari, Oskoui Farid. "Stress oxydatif, vieillissement et maladie de Parkinson." Bordeaux 2, 1997. http://www.theses.fr/1997BOR2M024.
Lefeuvre, Jocelyne. "Dépression, Dopamine et maladie de Parkinson." Bordeaux 2, 1991. http://www.theses.fr/1991BOR23034.
Laplace, Martine. "Radicaux libres et maladie de Parkinson." Bordeaux 2, 1996. http://www.theses.fr/1996BOR2P017.
Jourdes, Peggy. "Électrotransfert de gènes et effets du néovastat(R) dans les glioblastomes : approche pré-clinique de deux traitements de pathologies cérébrales." Université Joseph Fourier (Grenoble), 2002. http://www.theses.fr/2002GRE19012.
The treatment of neurodegenerative diseases and glioblastoma requires the development of new therapies such as gene therapy or new molecules synthesis. The transfection of central nervous system (CNS) cells or muscular cells aims to allow the expression in the long term of favorable factors for the etiologic treatment of the disease. We optimized the parameters of electrotranfer in the mice muscle (5*900V , 99æs, 1 Hz) and in the brain of mice and rats (10*600V, 99æs, 1Hz). The electrotransfer increases by 500 the rate of transgene in the muscle and by 700 to 1000 in the CNS. The voltages seem to be far from the applicable parameters in high frequency deep brain stimulation in Parkinson's disease. We revised the methodology applied with low frequency and we demonstrated the transfection of the rat CNS by high frequency stimulation (130 Hz) with a current intensity of 3 mA and a pulse width of 99 æs. So, we get closer to clinical parameters. As regards the treatment of the malignant glioblastoma, no conventional therapy turned out to be effective. The elaboration of Neovastatâ by Aeterna laboratories presents promising preclinical results. Indeed, this medicine which consists of active factors issued from the shark cartilage, is a natural antiangiogenic and antitumoror agent that possesses an important therapeutic potential
Souchay, Céline. "Exploration de la métamémoire dans le vieillissement normal, la maladie d'Alzheimer et la maladie de Parkinson." Tours, 2000. http://www.theses.fr/2000TOUR2019.
Jourdain, Vincent. "Effets de la neurostimulation dans la douleur chronique et la maladie de Parkinson." Thesis, Université Laval, 2010. http://www.theses.ulaval.ca/2010/27883/27883.pdf.
Damiano, Maria. "Rôle de la dysfonction mitochondriale dans deux maladies neurodégénératives, la Maladie de Huntington et la Maladie de Parkinson." Thesis, Paris 6, 2014. http://www.theses.fr/2014PA066584/document.
Mitochondrial dysfunction has been implicated in several neurodegenerative diseases and is correlated with augmented levels of intracellular oxydant stress. The mitochondrial defects observed in tissues from patients, as well as in animal and cellular models of Huntington’s and Parkinson’s diseases, suggest the implication of mitochondria in the pathogenesis of these diseases. The two projects discussed in this manuscript focus on the role of particular aspects of mitochondrial physiology in these diseases. By the first project we show the role of defective mitochondrial respiratory chain compex II in several rodent models of Huntington’s disease. By using a lentivirus-based gene transfert strategy we highlight the neuroprotective potential of the striatal overexpression of the subunits of complex II. The second project focus on Parkin and PINK1, two proteins implicated in the autosomal recessive, hereditary forms of Parkinson’s disease and in mitochondrial quality control mechanisms, such as mitophagy. In a cellular model we show that the two proteins facilitate Drp1-dependent mitochondrial fission. We show that Parkin may facilitate the signaling pathways controlling the activity of the pro-fission protein Drp1. This effect is probably indirect and mostly PINK1-independent. On the contrary, in mitochondrial depolarization conditions, by FRET (Förster Resonance Energy Transfer) a direct spatial coordination of Parkin, PINK1 and Drp1 is observed, which seems to be determinant for the efficiency of mitophagy. My projects shed new light on pathogenic mechanisms and open new perspectives in the research on these diseases
Modolo, Julien. "Modélisation et analyse mathématique des effets de la stimulation cérébrale profonde dans la maladie de Parkinson." Bordeaux 2, 2008. http://www.theses.fr/2008BOR21540.
High-frequency deep brain stimulation (DBS) is a symptomatic treatment that relieves motor disorders of Parkison's disease (PD). However, physiological mechanisms underlying symptoms improvements are still poorly known. We present a nex model consisting in a two-dimensional population based model describing the activity over time of a neuronal population. This model is used to explore the dynamics of the complex formed by the subthalamic nucleus (STN) and the external segment of the Globus Pallidus (GPe). We show that a resonance phenomenon appears to explain differencial effects of DBS depending on the stimulation frequency. Then, we propose a new physiological mechanism that could underlie the effects of DBS : stimulation-induced functional decoupling (SFID). This mechanism is discussed using simulation results, as well as experimental and clinical observations
Temsamani, Hamza. "Etude des effets neuroprotecteurs des stilbènes de la vigne sur la maladie de Parkinson." Thesis, Bordeaux, 2015. http://www.theses.fr/2015BORD0433/document.
Parkinson’s disease is one of the most spread neurodegenerative diseases in the world. Post mortem analyses have put in evidence small inclusion bodies in patient’s brain, composed of α-synuclein fibrils. Several studies attempted then to identify compounds that could inhibit α-synuclein aggregation, as its aggregation is linked to its toxicity. Still, numerous active compounds need to be identified in order to put on relief shared active structures that could lead to a potent drug design. Stilbenes are phenolic compounds that often display interesting health-related biological activities. In this study, the anti-aggregative behavior of stilbenes monomers (resveratrol, piceatannol) and oligomers such as ampelopsin and isohopeaphenol was assessed. The results put on evidence stilbene propensity to inhibit α-synuclein aggregation and provide an insight into their inhibition mechanisms
Coulombe, Katherine. "Effets des acides gras polyinsaturés oméga-3 dans deux modèles murins de maladie de Parkinson." Master's thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/28207.
Parkinson's disease (PD) is an incurable neurodegenerative disease affecting the integrity of the dopaminergic system of patients. Several studies suggest that lifestyle and eating habits influence the onset and progression of the disease. A diet rich in omega-3 polyunsaturated acid (n-3 PUFA) shows protective effects on the dopaminergic system and a decrease of the neuronal degeneration in the substancia nigra (SNpc). The hypothesis that we propose is that a diet enriched in n-3 PUFA would slow the progression of the disease in a 6-hydroxydopamine (6-OHDA) mice model and influence the presence of alpha-synuclein aggregates (αSyn) in the brain of a transgenic mice overexpressing the human αSyn, Thy1-αSyn mice. Our results show partial neurorecuperation of the dopaminergic system with an enriched diet. The n-3 PUFAs show little influence on the expression of αSyn levels. Altough, they seem to modulate the levels of different synaptic proteins in transgenic mice and increase mice longevity.
Tremblay, Christina. "Effets de la stimulation cérébrale sur la compréhension des métaphores dans la maladie de Parkinson." Doctoral thesis, Université Laval, 2015. http://hdl.handle.net/20.500.11794/25855.
Different language deficits are often observed in Parkinson's disease (PD), including difficulties to understand metaphors. These difficulties seem to be associated with a decreased activation of the dorsolateral prefrontal cortex (DLPFC), possibly caused by fronto-striatal network dysfunctions. Polysemy (the property of a word to have multiple related meanings) is a linguistic factor intrinsic to the composition of a metaphor and could have an impact on this deficit, but its influence is unknown. Metaphor comprehension is also likely to be influenced by different brain stimulation technics that may have an impact on the fronto-striatal loops and the DLPFC, including Deep Brain Stimulation (DBS) (a surgical treatment producing subcortical continuous electrical stimulation) and Transcranial Magnetic Stimulation (TMS) (a noninvasive experimental approach that can influence brain activity by transient magnetic pulses). According to several studies evaluating both the effects of electrical stimulation and surgery, DBS generally impairs language abilities. However, differentiated effects of electrical stimulation on language, including metaphor comprehension, are still unclear. Additionally, TMS could potentially improve the DLPFC dysfunction, but its effects on metaphor comprehension deficits in PD have never been evaluated. Thus, the aim of this thesis is to evaluate the effects of DBS and TMS on metaphor comprehension in PD. The results of the first study, evaluating the influence of polysemy, showed how to properly control the impact of this factor when evaluating metaphor comprehension in this disease. In the second study, which focused on DBS effects, we observed no impact of electrical stimulation on metaphor comprehension. Finally, in the third study, the application of a particular TMS protocol on the DLPFC improved metaphor comprehension in a participant with PD. Overall, this thesis has contributed to advance knowledge on metaphor comprehension in PD and on the influence of different brain stimulation technics on this ability. It also provided new neuroanatomical hypotheses that could be used in future studies.
Kreisler, Alexandre. "Effets des fibrates et des statines dans la maladie de Parkinson : des modèles expérimentaux au patient." Lille 2, 2007. http://www.theses.fr/2007LIL2S024.
COUSINIE, VERONIQUE. "Comparaison de la bromocriptine et de la levodopa dans le traitement de premiere intention de la maladie de parkinson : comparaison des effets secondaires de la leovodpa chez des patients traites par levodopa ou bromocriptine plus levodopa." Toulouse 3, 1991. http://www.theses.fr/1991TOU31059.
Boukhzar, Loubna. "Contribution à l'étude du rôle de la Sélénoprotéine T dans la maladie de Parkinson." Thesis, Normandie, 2017. http://www.theses.fr/2017NORMR002/document.
Neurodegenerative diseases are progressive pathologies that affect the nervous system, causing the death of nerve cells. The best known and most frequent are Alzheimer's and Parkinson's disease, but there are others. All these diseases are characterized by the progressive loss of neurons of the nervous system, leading to cognitive, motor or perceptual complications. Parkinson's disease (PD) is caused by the degeneration of dopaminergic neurons of the substantia nigra and their nerve endings that normally release dopamine into the striatum. The two main risk factors common to neurodegenerative diseases are age and oxidative stress. Oxidative stress plays a central role in the pathophysiology of PD, but the mechanisms involved in controlling this stress in dopaminergic cells are not fully elucidated. Many studies show that selenoproteins play a central role in the control of redox homeostasis and cell protection, but the precise contribution of members of this family of proteins during neurodegenerative diseases is still unknown. Previous studies performed in our laboratory have uncovered the essential role of a new selenoprotein, selenoprotein T (SelT) in the processes of neuronal differentiation, but the role of this selenoprotein in neuroprotection was not known. We first showed that SelT, whose gene knock-out is lethal during embryogenesis, exerts a potent thioredoxin-like oxidoreductase activity. In a cellular model of dopaminergic neurons, represented by SH-SY5Y neuroblastoma cells, modification of SelT expression affects the level of oxidative stress and cell survival. Treatment of wild-type mice by neurotoxins targeting dopaminergic neurons such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or rotenone induced massive expression of SelT in the nigro-striatal system, suggesting that SelT could protect these neurons under conditions of degeneration. On the other hand, this same treatment given in mice invalidated for SelT in the brain caused a parkinsonian syndrome with the appearance of motor symptoms, thus confirming that the presence of SelT must participate in the protection of dopaminergic neurons under conditions mimiking PD. The observed motor symptoms are associated with oxidative stress and marked degeneration of dopaminergic neurons. Similarly, we observed a decrease in the active form of tyrosine hydroxylase, resulting in reduced dopamine levels in the striatum of invalidated and neurotoxin-treated mice. These data show that SelT is essential for the survival and functionality of dopaminergic neurons in vitro and in vivo under the conditions of neurodegeneration mimicking PD. Finally, in patients with PD, we observed a considerable increase in SelT levels in the caudate-putamen but not in other cerebral structures. Together, these results uncovered the activity of a novel thioredoxin-like enzyme that protects dopaminergic neurons against oxidative stress and prevents the early onset of severe motor symptoms in animal models of PD. Our data indicate that selenoproteins such as SelT, whose levels are increased in PD play a crucial role in protecting dopaminergic neurons against oxidative stress and cell death, thus paving the way for the development of new neuroprotection strategies targeting these proteins in PD
Tasselli, Chevalier Maddalena. "Effets de la roténone sur le système nerveux entérique." Nantes, 2014. http://archive.bu.univ-nantes.fr/pollux/show.action?id=b5034f4f-3458-46e3-a560-4c40d745e169.
Parkinson’s disease (PD) is the second disease in term of frequency: its prevalence is estimated to be 1,8% of the population aged over 65. PD is a specific neurodegenerative pathology targeting the dopaminergic neurons of the substantia nigra pars compacta and associated with the presence of intracellular proteins aggregates, termed Lewy bodies in the remaining surviving neurons. Remarquably alpha-synuclein, a protein involved in familial forms of PD, has been described to be the main component of Lewy bodies. The lack of dopamine is mainly responsible of the motors symptoms, nonetheless recent studies showed the possibility of an extra-nigral injury. Recently the enteric nervous system (ENS) has received a particular interest for different reasons: (i) it has a functional and anatomical organisation similar to the CNS, (ii) it is involved in the pathological process before the CNS, (iii) it is responsible of digestive disorders. It has been proposed that PD results from a combination of genetic and environmental factors. Among those environmental toxins, rotenone has been proposed to play a central role in the pathophysiological process. It may be able to penetrate the organism either by respiratory and digestive tract. During my thesis my work has been focused the effects of rotenone on the ENS both in vitro using a rat primary culture and in vivo using an oral intoxication animal model
Sarr, Mamadou Moustapha. "Effets de la L-Dopa et de la stimulation du noyau subthalamique et étude comparée des deux thérapies sur la coordination pneumo-phonique dans la dysarthrie parkinsonienne." Aix-Marseille 2, 2009. http://www.theses.fr/2009AIX20723.
The study’s aim was to determine Parkinson’s disease (PD) effect on pneumophonic coordination (PPC) and to evaluate and compare L-dopa and subthalamic nucleus (STN) stimulation effects on PPC. Intra-oral pressure (IOP), oral air flow (OAF) and laryngeal resistance (LR) were measured with EVA2 system at the six /p/ of the sentence “Papa ne m’a pas parlé de beau-papa” produced by 51 patients and 50 healthy subjects. PD decreases IOP and OAF and increases RL variability. IOP reduction and LR increase at the sentence onset led to patients’ compensation with vocal abuse and thus induced a discrete OAF increase during the course of the sentence. The comparative study carried out with 24 patients recorded in four conditions ON/OFF L-dopa and STN Stimulation showed marked similar therapy effects even if the patients ON treatment did not reach the control subjects’ level. Temporal study according to PD duration and post surgical delay did not show sensitive parameter variations in time but therapy effects were persistent except for LR. So LR seems less responsive to therapy effects
Funkiewiez, Aurélie. "Cognition et comportement dans la maladie de Parkinson : effets de la L-dopa et de la stimulation du noyau subthalamique." Grenoble 2, 2004. http://www.theses.fr/2003GRE29054.
Drouot, Xavier. "Effets fonctionnels de la stimulation électrique du cortex moteur dans un modèle primate de la maladie de Parkinson." Paris 12, 2005. https://athena.u-pec.fr/primo-explore/search?query=any,exact,990002532020204611&vid=upec.
We conducted a preclinicai study of electrical interference in the primary motor cortex using a chronic MPTP primate model in which dopamine depletion was progressive and reguiariy documented using 18-F-DOPA positron emission tomography (PET). Compared to the OFF condition, 130 Hertz motor cortex stimulation produced a significant increase in total distance moved and maximal velocity and significantly reduced akinesia and bradykinesia, in animais with moderate or severe 18-F-DOPA depletion, but flot in nondisabled animais. This benefit was associated with an increased metabolic activity in the suppiementarY motor area as assessed with 18-F-deoxyglucoSe PET, a normalization of mean firing rate in the internaI globus pallidus (GPL) and the subthalamic nucleus (STN) and a reduction o? synchronized oscillatory neuronal activities in these two structures. Motor cortex stimulation is a simple procedure to modulate subthalamo-pallidocortical loop and alleviate parkinsonian symptoms
Litim, Ahmed Nadhir. "Effets de médicaments gonadiques pour la neuroprotection du cerveau chez un modèle animal de la maladie de Parkinson." Doctoral thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/27469.
Parkinson’s disease (PD) is the most common neurodegenerative movement disorder and is likely to increase due to the aging population. There is no cure for PD and no disease-modifying drug available. A higher incidence of this disease is observed in men suggesting a possible neuroprotective effect of female sex steroids. In animal models of PD, beneficial protective effects of estrogen and progesterone have been reported while the androgenic gonadal steroids showed little or no neuroprotective activity. We explored the neuroprotective activity of drugs acting on the synthesis of steroids. Dutasteride and finasteride are inhibitors of 5α-reductase enzyme used in humans to treat various endocrine disorders. In the mouse model of PD injured with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), we found that dutasteride but not finasteride exhibits neuroprotective activity on dopamine (DA) neurotransmission of the brain. The mechanisms implicated in the neuroprotective effects of dutasteride have been further studied in intact and MPTP-lesioned mice. The analysis of motor behavior of these mice showed that treatment with MPTP, MPTP + dutasteride did not affect the motor behavior as expected with a low dose of MPTP to induce moderate injury modeling early stages of the disease. Our results suggest that dutasteride has neuroprotective effects on dopaminergic neurons and anti-inflammatory properties in the brain. These results suggest dutasteride as promising therapeutic drug for PD neuroprotection in the early stages of the disease. We have previously reported neuroprotection by progesterone on striatal DA in MPTP mice when administered before or 1 hour after the toxin. The results presented here suggest that progesterone can promote recovery of dopaminergic neurons when administered at an early stage (24h) but not at a late stage (5 days) after injury in male mice including through mitigation of neuroinflammation. These data highlight the need to develop disease-modifying therapies but also to provide personalized treatments by gender. Thus, the specific treatment options for each sex can be imagined such as the use of dutasteride in men and progesterone-based therapies for both sexes. However, additional studies are needed to optimize these therapies to get safer personalized treatments that would delay, prevent or treat PD.
Drouot, Xavier Palfi Stéphane. "Effets fonctionnels de la stimulation électrique du cortex moteur dans un modèle primate de la maladie de Parkinson." Créteil : Université de Paris-Val-de-Marne, 2007. http://doxa.scd.univ-paris12.fr:8080/theses-npd/th0253202.pdf.
Thèse électronique uniquement consultable au sein de l'Université Paris 12 (Intranet). Titre provenant de l'écran-titre. Bibliogr. f. 189-216.
Bleuse, Séverine. "Effet de l'âge et de la maladie de Parkinson sur les ajustements posturaux anticipateurs lors d'un mouvement d'antéflexion du bras." Lille 2, 2004. http://www.theses.fr/2004LIL2S014.
Execution of a voluntary movement, such as arm movement, is preceded by a sequence of postural modifications. These anticipatory postural adjustments are movement-specific and thus appear to be centrally organized prior to movement execution. They tend to minimize the potential disturbance of the forthcoming movement and allow equilibrium to be maintained during execution. The unilateral flexion performed during the upright human position imposes a vertical torque, center of pressure displacement and muscular activities. In our study, the subjects stood on a force platform, performed shoulder flexion of their right arm, to grasp a handle in front of them. Six conditions : self-paced at 3 different velocities (slow, medium, maximal), triggered by an auditory signal, loaded, all at maximal velocity ; in sixth condition, the arm was passively displaced by an experimenter. This work allowed to show the interest of biomechanical parameter : the vertical torque. A base of normative data of anticipatory postural adjustments have been performed in healthy subjects (young and elderly), to study postural preparation in subjects with Parkinson's disease. Moreover in these patients we analyzed effect of treatment (such as L-dopa and nucleus subthalamic stimulation ) on anticipatory postural adjustments
El, Manaa Wejdane. "Contrôle de la mitophagie dans la maladie de Parkinson : Dialogue fonctionnel entre XBP1 et PINK1." Electronic Thesis or Diss., Université Côte d'Azur (ComUE), 2019. http://theses.univ-cotedazur.fr/2019AZUR6004.
Parkinson's disease (PD) is a neurodegenerative disease characterized by progressive loss of dopaminergic neurons. PD-affected brains show consistent endoplasmic reticulum (ER) stress and mitophagic dysfunctions. The mechanisms underlying these perturbations and how they are directly linked remain poorly understood. XBP1 is a transcription factor activated upon ER stress after unconventional splicing by the nuclease IRE1 thereby yielding XBP1S while PINK1 is a kinase considered as the sensor of mitochondrial physiology and a master gatekeeper of mitophagy process. We show that XBP1S transactivates PINK1 in human cells, primary cultured neurons and mice brain, and triggers a pro-mitophagic phenotype that is fully dependent of endogenous PINK1. We also unravel a PINK1-dependent phosphorylation of XBP1S that conditions its nuclear localization and thereby, governs its transcriptional activity. PINK1-induced XBP1S phosphorylation occurs at residues reminiscent of those phosphorylated in substantia nigra of PD-affected brains. Overall, our study delineates a functional forward loop between XBP1S and PINK1 governing mitophagy that is disrupted in PD conditions
Abou-Hamdan, Mohamad. "Effets neuroprotecteurs des composés thiol : l'exemple de la pantéthine." Aix-Marseille 2, 2008. http://www.theses.fr/2008AIX20678.
Serret, Mathilde. "Élaboration d'un dispositif de danse-thérapie à expression primitive et évaluation de ses effets auprès de patients atteints de la maladie de Parkinson." Thesis, Université Côte d'Azur (ComUE), 2018. http://www.theses.fr/2018AZUR2011.
Recent studies have shown that dance may be an appropriate and effective strategy for improving motor and non-motor symptoms, as well as quality of life on individuals with Parkinson’s Disease (PD). Dance-Therapy through primitive expression (DTPE), as a mind-body therapy, may convey superior benefits, not only on physical areas but also on psychological and social ones. The main hypothesis is that Dance-Therapy will lead to greater gait and balance ability, an improved quality of life, will have psychological and social benefits and is an important component of a multidisciplinary approach to long-term management of PD.The first study, which lasted for two years, consisted of elaborating, observing and modifying the DTPE proposals in order to adapt them to the requirements of Parkinson's disease and to develop protocols of sessions in order to propose an innovative management of the disease.The second study, developed after a thorough literature review and which lasted seven months, made it possible to test the feasibility of such a study, to test a first main outcome (gait) and to evaluate the effects of the DTPE with the scales, which, after reviewing the studies on the subject, appeared to us to be the most relevant and well recognized in the medical community.The development of an original approach between Human and Social Sciences and Medicine can be used to feed the practices and care of patients by providing useful elements for the training of professionals and the organization of care. The thinking that has grounded the methodology of the studies developed in this thesis will contribute to fueling research and setting up new studies
Dellapina, Estelle. "Étude physiopathologique de la douleur dans la maladie de Parkinson : approches pharmacologique, en neuroimagerie et évaluation des effets de la stimulation cérébrale profonde du noyau sous-thalamique." Toulouse 3, 2012. http://thesesups.ups-tlse.fr/1758/.
One of the most disabling and frequent symptom of Parkinson's disease (PD) is pain. PD patients can suffer from different types of painful symptoms. In this work, we were interested in central neuropathic pain. Pathophysiological basis of this type of pain remains to clarify. A central modification of pain processing has been suggested in PD with a hypersensitivity to pain and abnormal activations of areas involved in pain processing in patients with PD. One hypothesis is that these abnormalities in pain perception could be related to central dopamine deficiency, one of the neuropathological hallmarks of Parkinson's disease. Indeed, basal ganglia have been shown to be involved in pain processing. This work evaluated the role of dopaminergic system in pain perception in two different ways: one evaluating the effect of a dopamine agonist on pain perception and the other testing the correlation between dopamine deficiency and clinical parameters of pain. Results showed that dopaminergic system is probably not involved in pain perception abnormalities and in the occurrence of central neuropathic pain in Parkinson's disease. Others monoaminergic systems, such as the noradrenergic system, could thus be involved and it would be interesting to test this hypothesis in future studies. The other part of our work showed that subthalamic deep brain stimulation had a significant effect on pain threshold, pain-induced activity in positron emission tomography and pain intensity in patients suffering from central neuropathic pain. Deep brain stimulation of this target could thus be an interesting treatment of pain in Parkinson's disease
Robelet, Sandra. "Effets de la DOPA-thérapie sur la réactivité des systèmes glutamatergiques à la perte des neurones dopaminergiques dans un modèle de la maladie de Parkinson chez le rat." Aix-Marseille 2, 2004. http://www.theses.fr/2004AIX22083.
Boraud, Thomas. "Physiopathologie des dyskinésies induites par les traitements dopaminergiques : approche électrophysiologique chez le singe traité au MPTP." Bordeaux 2, 1999. http://www.theses.fr/1999BOR2M014.
Rivest, Robert. "Étude des effets neurocomportementaux de la neurotensine et de peptides apparentes dans un modèle animal de la maladie de Parkinson." Mémoire, Université de Sherbrooke, 1988. http://hdl.handle.net/11143/11715.
Roy, Marc-André. "Effets de la L-DOPA et des autres principaux antiparkinsoniens sur le fonctionnement cognitif dans la maladie de Parkinson idiopathique." Doctoral thesis, Université Laval, 2017. http://hdl.handle.net/20.500.11794/27818.
Giguère-Rancourt, Ariane. ""Goal Management Training" : effets d'un programme d'entraînement des fonctions exécutives chez des patients atteints de la maladie de Parkinson idiopathique." Doctoral thesis, Université Laval, 2021. http://hdl.handle.net/20.500.11794/69591.
Parkinson's disease (PD) is a neurodegenerative disease characterised by resting tremor and rigidity. In addition to these motor symptoms of PD, other non-motor symptoms occur, such as cognitive deficits. Approximately 30% of PD patients develop Mild Cognitive Impairment (MCI) with executive dysfunction, that is, difficulties in executive functions. These functions are the ability to organize and coordinate thoughts, goal directed behaviors and to regulate emotions. Few treatments are actually available specifically for cognitive impairment in PD patients. Since medication development can take several years and cause adverse side effects, other non-pharmacological treatments may be useful in helping patients with PD-MCI. This thesis aims to evaluate two non-pharmacological approaches (cognitive training and psychoeducation), which were adapted to patients with PD-MCI. In order to meet certain limitations of previous studies, the Goal Management Training (GMT) training program was chosen for administration to PD-MCI patients with executive dysfunction. Another program was developed in form of psychoeducation on PD and various symptoms, coupled with mindfulness exercises. The first study intended to adapt the GMT program to PD-MCI population. With a multi baseline case study in a first patient, safety and acceptability were verified on several parameters (fatigue, psychological and behavioral symptoms, changes in medication or dosage and caregiver burden). The results show that GMT is safe and acceptable. In addition, it improves concerns about executive functions. The second study assessed the effects of the two programs (executive functions, quality of life, overall cognition) with a randomized - control study. Six patients received the adapted GMT, and six others received the combination of psychoeducation and mindfulness. The programs were administered at the home of each participant in the presence of the caregiver, in five sessions of 60-75 minutes, over five weeks. Various follow-up measures were taken at one, four and 12 weeks after the end of the intervention. The results show that both programs improved concerns about executive functions. They also reduced the number of errors made in an executive functions task, with a non-significant trend towards greater improvement in the GMT group. After four weeks, the group combining psychoeducation and mindfulness saw an improvement in quality of life, whereas scores of the GMT group were maintained. This study shows the interest of non-pharmacological approaches. Each program has its advantages and limitations depending on the profile of each participant. The third study aimed to include caregiver's data. During the second study, the caregivers of each participant answered questionnaires on the feelings of burden and distress. First, all data from the baseline, before randomization and interventions, were combined. The associations between clinical variables and variables in caregivers were assessed with a correlation matrix. Secondly, the effects of the two interventions were specifically evaluated on caregiver's measures. The results show there was no deterioration in feelings of burden and distress among caregivers for any of the groups, even if they had to invest time during the interventions. This study showed the importance of involving caregivers in the therapeutic process of PD-MCI patients. This thesis has shown the potential of two non-pharmacological approaches to improve concerns of patients with cognitive disorders. The three studies show limits, as well as strengths. Different theoretical and clinical recommendations regarding the intervention in people with PD-MCI can be considered.
Baldi, Isabelle. "Effets neurologiques centraux chroniques des expositions professionnelles aux pesticides." Bordeaux 2, 1998. http://www.theses.fr/1998BOR28621.
Cassar, Marlène. "Mécanismes moléculaires et de signalisation induits par le stress oxydatif dans des modèles in vivo de la maladie de Parkinson chez la drosophile : intoxication au paraquat et expression de l'α-synucléine". Phd thesis, Université Pierre et Marie Curie - Paris VI, 2012. http://tel.archives-ouvertes.fr/tel-00827809.
Le, Féron de Longcamp Amaury. "Troubles de la mémoire de travail et des fonctions attentionnelles dans le vieillissement normal et les maladies neurodégénératives." Caen, 2008. http://www.theses.fr/2008CAEN3107.
The main objective of this work was to increase the knowledge on visuo-spatial attentional functions and working memory in normal ageing (NA) and early stages of Parkinson (PD) and Alzheimer’s (AD) diseases. Firstly, we developed and validated in healthy young subjects a new approach based on the oculomotricity to quantitatively and qualitatively assess these cognitive functions; the educational level was also taken into account. By comparing various oculomotors spans with scores on standard neuropsychological tests, using principal-components analyses, we were able to reveal the cognitive strategies used by the subjects. A second study showed that impaired performances of healthy elderly subjects mainly affected working memory (both verbal and spatial), inhibition and divided attention. Moreover, elderly subjects developed compensatory mechanisms by monitoring most of their attentional and memory abilities. In a third study, we highlighted the attentional and working memory impairments that can be observed as soon as the early stages of PD and AD with predominant visuo-spatial deficits in the former. We also showed that visuo-spatial attentional capacities and working memory are much more affected in PD than in AD despite similar global cognitive deficiency. In addition, the cognitive strategies strongly differed between both groups of patients
Nafia, Imane. "Vulnérabilité différentielle des cellules mésencéphaliques au glutamate et au dysfonctionnement de ses transporteurs." Aix-Marseille 2, 2008. http://theses.univ-amu.fr.lama.univ-amu.fr/2008AIX22038.pdf.
Dopamine (DA) neurons degenerating in Parkinson disease (PD) highly express the neuronal glutamate transporter EAAT3, a major entry route of precursors of the antioxidant glutathione (GSH). Nigral depletion of GSH is one of the earliest biochemical events of PD, and could result from EAAT3 dysfunction. The hypothesis of a particular vulnerability of DA neurons to altered glutamate transport has been studied both in vitro and in vitro. My Ph. D. Thesis works showed that altered glutamate transport in mesencephalic cultures induces increase in extracellular glutamate concentration, GSH depletion and free radical production, leading both to gliotoxicity and neurotoxicity, with a preferential death of DA neurons. Altered glutamate transport induces oxidative death of astrocytes, excitotoxic death of non DA neurons, and specific death of DA neurons associating both oxidative and excitotoxic interdependent processes. The neurotoxicity induced by altered glutamate transport differs from that induced by glutamate. Moreover, altered glutamate transport exacerbates the NMDA toxicity selectively in DA neurons. Taken together, the in vitro data suggest that altered glutamate transport induces in DA neurons an oxidative stress which render them highly vulnerable to excitotoxicity. My results also showed that in vivo altered glutamate transport induces massive and dose-dependent loss of DA neurons of the substantia nigra pars compacta and formation of intracytoplasmic a-synuclein aggregates. Altogether, these data suggest a ‘metabolically’ crucial function of EAAT3 transporter in antioxidant defenses of DA neurons, and its dysfunction as a candidate mechanism for the neurodegeneration of DA neurons in PD
Damier, Philippe. "Vulnerabilite differentielle des neurones dopaminergiques dans la maladie de parkinson : un role du stress oxydatif et de l'environnement glial ?" Paris 6, 1996. http://www.theses.fr/1996PA066108.
Lemay, Simon. "Effets d'un traitement transdermique à la nicotine sur les troubles du mouvement et de la cognition dans la maladie de Parkinson /." Montréal : Université du Québec à Montréal, 2005. http://accesbib.uqam.ca/cgi-bin/bduqam/transit.pl?&noMan=24576824.
Aidi, Knani Sabrine. "Effets de la modulation des canaux potassium SK et Kv4 sur les déficits moteurs et cognitifs de la maladie de Parkinson." Thesis, Aix-Marseille, 2014. http://www.theses.fr/2014AIXM4777.
Parkinson's disease (PD) is a neurodegenerative disease associated to a loss of dopaminergic nigrostriatal pathway that innervates the basal ganglia (GB). The DA neuron degeneration in PD induces imbalance between dopaminergic transmission, GABAergic and glutamatergic resulting in impaired neuronal excitability leading to the onset of motor and non-motor symptoms. Potassium channels, Kv4 and SK, are extensively involved in the phenomenon of neuronal excitability. We addressed the question of whether further blockade of SK or Kv4 activity could restore normal GB function in vivo. In this aim, we used a neurotoxin, 6-hydroxydopamine (6-OHDA) to produce two lesional models of Parkinson's disease in rats that mimics the cognitive and emotional deficits of the early phase of PD (partial and bilateral striatal lesions) and the motor deficits observed in the late phase of the disease (total unilateral nigral lesion). Apamin from bee venom (systemic injection, 0.1-0.3 mg/kg) and AmmTX3 from scorpion venom (intrastriatal injection, 0.2-0.4 g) were chosen to block SK and Kv4 channels respectively.In a first study, apamin treatment partially reduced motor deficits in the cylinder test and the rotation induced by apomorphine. In the second study, the AmmTX3 also decreased parkinsonian motor deficits. This late toxin restored cognitive behaviors (short-term social and spatial memory) and emotion (anxiety).Taken together, these results underlie the importance of SK channels as modulators of neuronal excitability of Kv4 channels as players of the homeostatic responses, and more importantly, provide potential targets for adjunctive therapies for Parkinson's disease
Desmeules, Francis. "Analyse post-mortem de cerveaux de patients parkinsoniens après 11 et 12 ans de stimulation cérébrale profonde du noyau sous-thalamique." Master's thesis, Université Laval, 2020. http://hdl.handle.net/20.500.11794/70366.
Parkinson’s Disease (PD) is a neurodegenerative disorder affecting approximately 1% of people above 65 years old. Diagnosis is based on clinical evaluation, the patients typically presenting a combination of resting tremor, bradykinesia and muscular rigidity, sometimes accompanied by postural instability. For almost 30 years now, clinicians have been able totake advantage of an alternative therapy to alleviate PD motor symptoms when the medication is deemed ineffective or its side effects impair significatively the patient’s condition. This therapeutic approach is called deep brain stimulation (DBS). The surgery implies the permanent insertion of electrodes into deep nuclei of the brain, usually the subthalamic nucleus (STN), relying on stereotaxic landmarks to establish the optimal target. Electrodes are subsequently connected to a stimulator to induce a high frequency electric current locally, according to parameters established by the neurologist. This non-curative therapy improves patient’s quality of life and reduces the doses of dopaminergic analogues administered along with their side effects. The objective of this study is to identify the clinical,morphological and neurochemical changes induced by chronic STN-DBS. This case series will therefore focus on a detailed analysis of the brain of two PD patients who underwent DBS for 11 and 12 years, two of the longest stimulation durations ever reported in detail in the literature, in order to better understand the long-term changes induced by chronic exposure to electric fields. The ultimate goal is to correlate some of the anatomical and neurochemical changes to the clinical outcomes of the therapy. Various mechanisms will be proposed to improve the global understanding of deep brain stimulation to be able, in thelong-term, to target other brain structures in order to treat other neurological, psychiatric or cognitive disorders.
Rekaik, Hocine. "Mécanismes d'action de l'homéoprotéine Engrailed dans les neurones dopaminergiques adultes du mésencéphale." Thesis, Paris 6, 2016. http://www.theses.fr/2016PA066257/document.
Homeoproteins are a major class of transcription factors that exert some of their functions through non-cell autonomous activity, due to their ability to transfer between cells. Two of these homeoproteins, En1 and En2 (collectively Engrailed) are responsible for midbrain dopaminergic (mDA) neuron development, and maintenance during adulthood. En1+/- mice display a selective and progressive degeneration of the mDA neurons, reminiscent of Parkinson disease (PD). Engrailed infusion confers neurotection against cell death in several mouse models of PD, leading to the hypothesis that Engrailed could be implicated in the physiopathology of the disease. To dissect the mechanisms underlying Engrailed-mediated protection, the transcriptome of mDA neurons in En1+/- was analyzed. It was found that the loss of one En1 allele leads to severe alterations in the expression of DNA damage response and chromatin remodeling genes. The same alterations were detected and amplified in an acute mouse model of oxidative stress, suggesting that mDA neurons from En1+/- mice are less resistant to oxidative stress and, conversely, that Engrailed may protect them against oxidative stress. Indeed, Engrailed transduction into mDA neurons saves them from cell death and restores all DNA damage and epigenetic marks. A second mechanism neuroprotection by Engrailed concerns LINE-1 elements. These retrotransposons have the ability to create genomic instability through their endonuclease activity. Their direct repression by Engrailed could be part of a general protective activity against genomic instability
Lancelot, Mathilde. "Prise en charge de la maladie de Parkinson par stimulation cérébrale profonde : enjeux philosophiques d'un soin technologique." Thesis, Université de Paris (2019-....), 2019. http://www.theses.fr/2019UNIP7186.
Deep brain stimulation (an invasive neurosurgical technique consisting of implantation and activation of electrodes in a part of the brain) was developed in the late 1980s to treat some Parkinson's disease patients, for whom conventional drug therapy was losing its effectiveness. Since the early 2000s, this care practice has been extended to other pathologies, for which experimental protocols are still in progress. This dissertation questions the role and influences of this technological medical practice on care, care relationships and the discourses produced about them. In other words, we seek to understand, determine and analyze what this technological medical practice shapes, both epistemologically and existentially. Through this study, we ask what are the effects of this type of care, in the short and long term perspective, on medical practices, medical knowledge, care relationships and the people who experience it. How are these effects addressed in the clinical and (neuro)ethical literature? Are they in line with these experiences and the issues they raise?Our philosophical approach is based on the combination of observational work and inquiries in health services, and epistemological and anthropological reflection grounded in a corpus of many "foreign materials". The main objective of this work is to demonstrate how technological care, inserted in the treatment of a chronic neurodegenerative disease, complicates care relationships in the long term, while providing new perspectives
Bahdoudi, Seyma. "Etude des mécanismes cellulaires et moléculaires impliqués dans les effets neuroprotecteurs du gliopeptide OctaDecaNeuropeptide (ODN) dans un model murin de la Maladie de Parkinson." Thesis, Normandie, 2017. http://www.theses.fr/2017NORMR138/document.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by a progressive loss of loss of dopaminergic (DA) neurons within the substantia nigra pars compacta (SNpc). Different mechanisms are associated with the neuropathogenesis of PD including dysfunction of the mitochondrial respiratory chain, oxidative stress, apoptosis and neuroinflammatory processes. Octadecaneuropeptide (ODN) is a diazepam-binding inhibitor (DBI)-derived peptide, expressed by astrocytes, which protects neurons against oxidative cell damages and apoptosis in an in vitro model of PD. Nevertheless, its protective action in vivo has never been investigated. Therefore, the aim of the project of this thesis was to investigate whether intracerebroventricular (i.c.v) injection of ODN could prevent DA neuron degeneration in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD, and to explore the vulnerability of ODN precursor knockout (DBI KO) mice to MPTP-induced neurotoxicity. The results show that a single i.c.v injection of 10 ng/μl ODN, 1 h after the last systemic administration of MPTP, prevents the reduction of the number of tyrosine hydroxylase (TH)-positive cell bodies and fibers in the SNpc and striatum, respectively. Immunofluorescence imaging, Western blot analysis and Q-PCR studies revealed that ODN totally abolished MPTP-induced decrease of TH positive cells, mRNA expression and protein levels. This neuroprotective effect of ODN is accompanied by a reduction in the number of reactive astrocytes, an inhibition of the expression of pro-inflammatory genes such as interleukins (IL) IL-1β and IL-6, and a decrease of tumor necrosis factor -α. In addition, ODN blocks the inhibition of the anti-apoptotic Bcl-2 gene and the stimulation of Bax and caspase-3 expression induced by MPTP in the SNpc and striatum. ODN also reduces the accumulation of reactive oxygen species (ROS) and lipid oxidation products in DA neurons. Furthermore, DBI-/- mice exhibited more vulnerability to MPTP than wild-type animals (DBI+/+). Thus, ODN KO mice are more sensitive to MPTP-induced inflammatory and oxidative brain damages, suggesting that the endogenous OD may also be neuroprotective. These results indicate that, based on its anti-oxidative, anti-inflammatory and anti-apoptotic effect, the gliopeptide ODN could lead to the development of effective therapeutic agents for the treatment of cerebral injuries involving oxidative neurodegeneration
Cléren, Carine. "Effets de la L-DOPA, du piribédil et de l'inhibition du VMAT2 sur la neurotoxicité induite par le MPP+ ou la 6-OHDA, chez le rongeur." Rouen, 2002. http://www.theses.fr/2002ROUES036.
6-hydroxydopamine (6-OHDA)and 1-methyl-4-phenylpiridinium (MPP+) are two neurotoxins which injected in mice, induce marked lesions (>50%)of nigro-striatal dopaminergic neurons, thus constituting murine models of Parkinson's disease. In human, L-DOPA remains the best symptomatic treatment of this disease. We observed that an acute injection of L-DOPA in mice, worsened 6-OHDA induced toxicity while it prevented MPP+ induced toxicity. Contrary to 6-OHDA, MMP+ did not damage hypothalamic noradrenergic neurons
Decamp, Emmanuel. "Caractérisation des déficits cognitifs attentionnels et des fonctions exécutives centrales induits par administration de faibles doses de neurotoxines MPTP chez les singes macaques : effets de thérapies agissants sur les récepteurs nicotiniques." Rennes 1, 2007. http://www.theses.fr/2010REN1S141.
The cognitive deficit aspect of Parkinson’s disease has received significant attention over the last two decades due to its prevalence and its failure to respond to therapies that address motor deficits. The subject of this thesis is to further understand the nature of these cognitive deficits and to assess the potential therapeutic value of nicotinic drugs on the disease using the chronic low dose MPTP primate model. Using different behavioral assays, we showed that CLD MPTP animals display a broad deficit in attention and in central executive functions. We also demonstrated that attentional deficits may be the main cause to deficits previously observed in working memory. Following these results, we tested nicotine and a sub-type selective agonist for their effects on attention and central executive functions. Both agonists improved performance in the tasks assessing attention, but only the subtype-selective agonist improved central executive functioning. We hypothesized that this difference in effect may be due to the specific receptors targeted by the selective agonist or may be caused by its action at the level of other receptors such as histaminergic. Finally, we studied the effects of dopaminergic and nicotinic therapies on working memory and attention. We found that the dopaminergic therapy most commonly used in the clinical population (levodopa) impaired the level of performance of MPTP-treated non-human primates, and the adjunction of nicotinic agents to levodopa counteracted the negative effects of dopaminergic therapy. These results are in accordance with some recent theories that describe deficits induced by dopamine, such as the “dopamine overdose” hypothesis
Thomas, Ollivier Véronique. "Analyse de la mémoire procédurale à travers l'étude du vieillissement normal et pathologique." Rennes 2, 1997. http://www.theses.fr/1997REN20025.
Cohen and Squire in 1980 introduced a distinction between "declarative" and "procedural" memories in structural models of human memory. Ten years later, Squire renamed procedural memory "non-declarative memory", which expresses a set of distinct capabilities whose only shared characteristic is precisely this "non-declarativeness". The aim of this study was to sharpen the definition criteria of one component of non-declarative memory, precisely the so-called procedural component, by studying it in situations of normal and pathological ageing. As a first step, we focussed on the distinction between the way knowledge is expressed and knowledge in itself. We studied the effect of motor activity on memorizing simple sentences describing actions. Results did not elicit any effect of pathology, action learning improved performance in Parkinsonian as well as healthy elderly subjects. We then analysed learning and performance preservation in more complex tasks based on a set of fixed rules. Results showed that performance is not linked to the type of knowledge and that learning difficulties mainly affect the learning phase in normal and pathological ageing. We then tested the hypothesis that executive functions play an important role in learning difficulties by varying the level of utilization of such capabilities in various tasks. Results clearly showed that performance depends on the level of involvement of these functions in elderly subjects and Parkinsonian patients. Analysing the whole set of results led us to proposing a more comprehensive definition of procedural memory, with the possible contribution of explicit memory in the early phases of learning
Forestier, Anne. "Effets du peptide Amyloïde-ß, caractéristique de la maladie d'Alzheimer, sur les systèmes de réparation de l'ADN." Phd thesis, Université de Grenoble, 2011. http://tel.archives-ouvertes.fr/tel-00680083.
Assous, Maxime. "Modèle progressif de la maladie de parkinson après dysfonctionnement aigu des transporteurs du glutamate dans la substance noire chez le rat." Thesis, Aix-Marseille, 2013. http://www.theses.fr/2013AIXM4034/document.
Parkinson's disease (PD) is characterized by the progressive degeneration of substantia nigra (SN) dopaminergic neurons. Central players in PD pathogenesis, including mitochondrial dysfunction and oxidative stress, might affect the function of excitatory amino acid transporters (EAATs). Here, we investigated whether acute EAATs dysfunction might in turn contribute to the vicious cycles sustaining the progression of dopamine neuron degeneration. PDC application on nigral slices triggered sustained glutamate-mediated excitation selectively in dopamine neurons. In vivo time-course study (4-120 days) revealed that a single intranigral PDC injection triggers progressive degeneration of exclusively dopamine neurons with unilateral to bilateral and caudorostral evolution. This degenerative process associates GSH depletion and specific increase in γ-glutamyltranspeptidase activity, oxidative stress, excitotoxicity, autophagy and glial reaction. The anti-oxidant N-acetylcysteine and the NMDA receptor antagonists ifenprodil and memantine provided significant neuroprotection Transient compensatory changes in dopamine function markers in SN and striatum accompanied cell loss and axonal dystrophy. Motor abnormalities (hypolocomotion and forelimb akinesia) showed late onset, when ipsilateral neuronal loss exceeded 50%. These findings outline a functional link between EAATs dysfunction and several PD pathogenic mechanisms and pathological hallmarks, and provide the first acutely-triggered rodent model of progressive parkinsonism