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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Caractérisation multiparamétrique des neurones du hilus du gyrus denté chez la souris

Leclerc, Clémence 12 October 2012 (has links) (PDF)
Dans le hilus du gyrus denté de l'hippocampe, les cellules moussues excitatrices et les interneurones GABAergiques constituent des acteurs clés du réseau. Cependant, en raison en partie de leur grande diversité, la fonction des interneurones GABAergiques du hilus dans la physiologie du gyrus denté reste peu détaillée. Nous avons utilisé des souris transgéniques GAD67-GFP, exprimant la GFP sous le contrôle du promoteur de la GAD67, et évalué les densités de neurones GABAergiques marqués pour la Calretinine (CR), Parvalbumine (PV), Somatostatine (SOM), Neuropeptide Y (NPY) et l'oxyde nitrique synthase (NOS-1) dans le hilus et la couche granulaire. Pour mieux caractériser les différentes populations d'interneurones, nous avons caractérisé les propriétés de 123 neurones en utilisant la technique de RT-PCR sur cellule unique sur des tranches de cerveaux de souris C57Bl6 âgées de 2 à 3 mois. Une analyse non supervisée en clusters basée sur 18 paramètres électrophysiologiques et 7 paramètres moléculaires a clairement mis en évidence un cluster de cellules moussues excitatrices (n=67) et 3 clusters de cellules GABAergiques (n=56). Les deux premiers clusters d'interneurones GABAergiques comprennent des neurones (n=18 et n=16) qui co-expriment le NPY et la SOM mais se différencient clairement par leurs propriétés élcetrophysiologiques. Le troisième cluster d'interneurones comprend des neurones à décharge rapide exprimant soit la PV (n=9) soit la NOS-1 (n=13). Cette caractérisation multiparamétrique supporte l'existence de classes fonctionnelles distinctes parmi les interneurones GABAergiques du gyrus denté
2

NEUROPROTECTIVE EFFECTS OF POSTINJURY LITHIUM TREATMENT: DETERMINING THE OPTIMAL DOSING PARADIGM AND ASSESSING POTENTIAL MECHANISMS OF ACTION

Eakin, Katharine 10 May 2010 (has links)
Traumatic brain injury (TBI) has a dramatic impact on our society in terms of mortality, morbidity, and inherently high financial costs. Formidable research efforts are being addressed to the identification of neuroprotective agents capable of ameliorating the neurological outcome after TBI. Preclinical studies have recently demonstrated lithium to be a promising neuroprotective agent for both acute ischemic brain injury and chronic neurodegenerative disease. In light of these encouraging data, we designed a lateral fluid-percussion injury (FPI) study aimed at investigating the role of early post-traumatic administration of lithium as a strategy for reducing TBI-induced motor and cognitive deficits. The optimal dose of this agent and the time window for its administration have been determined on the basis of data derived from the assessment of motor and cognitive functioning in experimental animals, as well as from the stereological quantification of neuronal survival (PID 7) within the CA3 and hilar regions of the hippocampus ipsilateral to the FPI. In addition, we attempted to elucidate the mechanisms underlying the neuroprotective properties of this drug via western blot analysis of levels of the pro-apoptotic marker caspase-3 (PID 1, 7) and two neuroplasticity markers, growth associated protein-43 (GAP-43) and brain-derived neurotrophic factor (BDNF) (PID 1, 7, 21). Our findings indicate that low-dose lithium chloride (0.125 or 0.25 mmol/kg), given either 30 min or 8 hr after lateral FPI significantly ameliorates injury-induced cognitive and motor impairment. Specifically, cell survival in the CA3 region of the hippocampus of the injured lithium-treated animals (but not in the hilus) was significantly increased compared to injured vehicle-treated animals. Western blot analyses revealed a significant increase in GAP-43 levels on PID 7 in injured animals when treated with lithium, indicating a possible mechanism for lithium-induced neuroprotection. In contrast, BDNF levels were relatively unchanged until PID 21, and caspase-3 activation was not observed at all, suggesting that these proteins play less significant roles in the observed neuroprotective effects of lithium treatment after lateral FPI. Early administration of lithium, within 8 hours after TBI, holds promise as an effective therapy to ameliorate postinjury neurobehavioral deficits and warrants further investigation in clinical TBI studies.

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