CONICET | Buscador de Institutos y Recursos Humanos

Brain aging is associated with a progressive increase in the incidence of neurodegenerative diseases and deterioration of spatial learning and memory in aging rats (AR) and human. This makes this rodent species a suitable model to evaluate therapeutic strategies of potential value for correcting age-related cognitive deficits. Adult bone marrow-derived MSCs (BM-MSCs) have been reported as potential candidates for treatment of neurodegenerative disorders.Here, we investigated the therapeutic potential of MSCs to treat cognitive impairment in AR. Dil-labeled human BM-MSCs were intracerebroventricularly bilaterally injected to 27-month-old female rats. Experimental subjects were divided in 3 groups: Young-intact, Senile-intact and Senile-MSC. Using the Barnes maze we assessed hippocampus-dependent learning and spatial memory before and after cell injection. Also, we assessed recognition memory with the Novel Object Recognition test. Additionally, we performed time-course studies for MSCs integration and viability in the brain and assessed a set of hippocampal cell markers.MSC therapy increased goal hole exploration activity in senile rats as compared with intact counterparts. Immature neuron number in the hippocampal dentate gyrus was higher in treated animals. Time course studies (24 days) revealed that MSCs integrated into ependymal cell layer and even in brain parenchyma.The results suggest that MSC therapy partially reverse the decline in cognitive performance that occurs in AR and improves a number of morphological parameters in the hippocampus. We conclude that adult stem cells are a suitable biological tool for the treatment of age-related neurodegeneration.