NMDA receptor antagonist treatment increases the production of new neurons in the aged rat hippocampus

The production of new neurons declines during adulthood and persists, although at very low levels, in the aged hippocampus. Since neurogenesis in young adults has been related to learning and memory, its reduction may contribute to the age-related impairments in these abilities. Adrenalectomy (ADX) enhances neurogenesis in the aged hippocampus, although it also induces neuronal cell death. Since the administration of an NMDA receptor antagonist enhances neurogenesis in young adult rats without deleterious morphological effects, we have tested whether neurogenesis could be reactivated in aged rats. Our study shows that cell proliferation, cell death, neurogenesis and the number of radial glia-like nestin immunoreactive cells decrease in middle-age (10 months) and remain very low in the aged hippocampus. Injection of the NMDA receptor antagonist to aged rats increases significantly the number of proliferating cells, new neurons and radial glia-like cells in the hippocampus.