Obiettivo Huntington’s disease (HD) is an inherited neurodegenerative disease, which has no cure, resulting from the mutation of the gene coding for huntingtin protein (htt). Clinically, HD patients present with progressive involuntary spasmodic movements and cognitive impairments. Post-mortem studies of HD patients reveal severe atrophy of the striatum, reflecting a selective neuronal loss of medium spiny neurons (MSNs). The path leading to MSNs death remains unknown. Conversely, astrocytic dysfunction might be a causal factor leading to HD pathogenesis. Astrocytes play 2 key roles in neuronal survival implicating glutamatergic transporters: supplying energy to the neurons (through a glycolytic flux) and regulating synaptic activity (mainly glutamatergic); and yet, both glucose consumption and glutamate regulation are altered in HD. To further study the specific role of astrocytes in the pathogenesis of HD, the host laboratory developed, using a lentiviral–based approach, the first in vivo mouse model which selectively expresses mutant htt in astrocytes. The main objective of this proposal is to gain new insights into the specific effect of astrocyte mutant htt expression on glutamate transporters and glycolytic metabolism. This objective will be achieved by pursuing a comprehensive characterization of this novel model (behavioral and neuropathological analyses using a stereological approach and detailed cell morphology analysis) and monitor the astrocytic function by combining techniques mastered by the applicant (electrophysiology) and by the host laboratory (glutamate receptors regulation and glucose utilization). Furthermore, defining the implication of altered astrocytes on neuronal loss would shed the light on the role of astrocytes in other neurodegenerative diseases. Campo scientifico natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencesgeneticsmutation Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2009-IIF - Marie Curie Action: "International Incoming Fellowships" Invito a presentare proposte FP7-PEOPLE-2009-IIF Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IIF - International Incoming Fellowships (IIF) Coordinatore COMMISSARIAT A L ENERGIE ATOMIQUE ET AUX ENERGIES ALTERNATIVES Contributo UE € 223 230,40 Indirizzo RUE LEBLANC 25 75015 PARIS 15 Francia Mostra sulla mappa Regione Ile-de-France Ile-de-France Paris Tipo di attività Research Organisations Contatto amministrativo Olivier Leroy Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
