Astroglial expression of erythropoietin as a potential support of neuronal survival in the hippocampus during epileptogenesis in adult rats
Résumé
Brain erythropoietin (Epo) provides substantial trophic support to neurons during both development and mild injury in adults. Moreover, exogenously administered Epo has been shown to reduce neuronal degeneration in various models of brain disorders. However, endogenous Epo system in basal conditions and its reactivity during pathological processes has received little attention. Here, we present for the first time the accurate in situ distribution of both Epo and Epo receptor (Epo-R) in the adult rat hippocampus in basal conditions, and reveal that Epo-R is expressed by a large majority of neurons, while Epo expression is restricted to some neuronal populations. Following pilocarpine-induced status epilepticus (Pilo-SE), Epo is induced in numerous astrocytes. Hippocampal areas where astroglial Epo induction is the greatest exhibit a pattern of delayed neuronal death. The evidence that enhanced Epo-mRNA is preceded by an increase in transcript levels of HIF-1Α, the regulatory sub-unit of its transcription factor Hypoxia-Inducible Factor-1 (HIF-1), argues in favor of the hypothesis that hypoxic/ischemic insult occurs in the hippocampus following Pilo-SE and may reasonably be proposed as a cause of neurodegeneration during epileptogenesis. This in situ analysis of both Epo/Epo-R and neuronal degeneration provides fundamental information on the ways Epo system may adapt to noxious microenvironment associated to epileptogenesis in order to support neuronal survival.