Erythropoietin Promotes Neural Plasticity and Spatial Memory Recovery in Fimbria-Fornix-Lesioned Rats

Abstract

Background. Erythropoietin (EPO) upregulates the mitogen activated protein kinase (MAPK) cascade, a central signaling pathway in cellular plastic mechanisms, and is critical for normal brain development. Objective. We hypothesized that EPO could modulate the plasticity mechanisms supporting spatial memory recovery in fimbria-fornix-transected animals. Methods. Fimbria-fornix was transected in 3 groups of rats. Seven days later, EPO was injected daily for 4 consecutive days within 10 minutes after training on a water maze task. Results. Our results show that EPO injections 10 minutes after training produced a substantial spatial memory recovery in fimbria-fornix-lesioned animals. In contrast, an EPO injection shortly after fimbria-fornix lesion surgery does not promote spatial-memory recovery. Neither does daily EPO injection 5 hours after the water maze performance. EPO, on the other hand, induced the expression of plasticity-related genes like arc and bdnf, but this effect was independent of training or lesion. Conclusions. This finding supports our working hypothesis that EPO can modulate transient neuroplastic mechanisms triggered by training in lesioned animals. Consequently, we propose that EPO administration can be a useful trophic factor to promote neural restoration when given in combination with training.