Restorative effects of human mesenchymal stem cell therapy on spatial memory in senile rats

LÓPEZ-LEÓN M ; ZAPPA F; GARCIA MG; MOREL GR; MAZZOLINI G; REGGIANI PC; GOYA RG

Congreso; Congreso de la Federación de Sociedades de Neurociencia de Lationoamérica y el Caribe.; 2016

Brain aging is associated with a progressive increase in the incidence of neurodegenerative diseases and deterioration of spatial learning and memory in aging rats and humans, which makes this rodent species a suitable model to evaluate therapeutic strategies of potential value for correcting age-related cognitive deficits. Since adult bone marrow-derived mesenchymal stem cells (BM-MSCs) have been reported as potential candidates for the treatment of neurodegenerative disorders, we investigated the therapeutic potential of BM-MSCs to treat cognitive impairment in senile rats. Dil-labeled human BM-MSCs were intracerebro-ventricularly bilaterally injected to 27-month-old female rats. Experimental subjects were divided into 3 groups: Young-intact (3 months), Senile-intact and Senile-MSC. Using the Barnes maze we assessed hippocampus-dependent learning and spatial memory before and after cell injection. Additionally, we performed time-course studies for MSCs integration and viability in the brain and assessed a set of hippocampal cell markers. BM-MSC therapy increased goal hole exploration activity in senile rats as compared with intact counterparts. Immature neuron number in the hippocampal dentate gyrus (DG) fell sharply in the old animals as compared with young counterparts. Immature neuron number in the DG of intact and MSC-treated old rats was comparable. Time course studies (24 days) revealed that BM-MSCs integrated into ependymal cell layer and occasionally in the brain parenchyma.The results suggest that BM-MSC therapy partially reverses the decline in cognitive performance that occurs in senile rats whereas the impact of the treatment on hippocampal morphology, which is still under analysis, has not yet revealed significant effects. We conclude that human BM-MSC are a promising biological tool for the treatment of age-related spatial memory deficits.