L'érythropoïétine et l'enrichissement du milieu de vie en cage Marlau™ protègent les populations neuronales et la fonction cognitive chez le rat épileptique
Auteur / Autrice : | Raafat P. Fares |
Direction : | Laurent Bezin |
Type : | Thèse de doctorat |
Discipline(s) : | Neurosciences |
Date : | Soutenance le 22/12/2009 |
Etablissement(s) : | Lyon 1 |
Ecole(s) doctorale(s) : | École doctorale Interdisciplinaire Sciences-Santé (Villeurbanne ; 1995-....) |
Partenaire(s) de recherche : | Laboratoire : Laboratoire de physiologie intégrative cellulaire et moléculaire |
Jury : | Président / Présidente : Philippe Ryvlin |
Examinateurs / Examinatrices : Didier Lagarde, Claire Rampon, Jean-Jacques Risso | |
Rapporteurs / Rapporteuses : Mireille Lerner-Natoli, Marcello Solinas |
Résumé
Patients with epilepsy often suffer debilitating cognitive and psycho-affective disorders.In some cases, epilepsy is associated to neurodegenerative processes that are the targetof certain therapeutical agents. Today, erythropoietin is considered as one of the most promising neuroprotective agents. In addition, an increased body of studies provides evidence that enrichment (or complexity) of housing decreases the cerebral vulnerabilityin the context of diverse brain insults. In this thesis, we demonstrate: 1) in a model ofepilepsy with large neuronal lesions, that erythropoietin protects the most vulnerable neuronal populations to excitotoxic injury, at the only condition that neuronal expression of its receptor is optimized prior to the primary insult causing epilepsy; 2) in a model of epilepsy associated with faint neuronal lesions that: i) erythropoietin prevents anxietyand impaired spatial learning and memory, ii) enriched housing in Marlau™ cages is moreefficient than erythropoietin, and iii) erythropoietin treatment abolishes beneficial effectsof enriched housing. These results, obtained in animal models of epilepsies associatedwith cognitive disorders establish that beneficial effects of a potential therapeutic agentmay rely on quality of life