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

LOPEZ-LEÓN M; ZAPPA VILLAR F; GARCÍA M; MOREL GR; MAZZOLINI G; GOYA RG; REGGIANI PC

CABA

Congreso; 2nd FALAN congress; 2016

IBRO-FALAN

Brain aging is associated with a progressive increase in the incidence of neurodegenerative diseases and deterioration of spatial learning and memory in both aging rats (AR) and humans. This makes this rodent species a suitable model to evaluate therapeutic strategies of potential clinical value for correcting age-related cognitive deficits. In a previous study, we demonstrated that while target-seeking activity and learning ability decrease in aged females rats, spatial memory only declines in the longer-term tests. The reduction in neuroblast number and astroglial arborescence complexity in the dorsal hippocampus are likely to play a role in the cognitive deficits of AR. We also observed that the number of immature neurons (doblecortin-positive cells) fell markedly with age in the hippocampal dentate gyrus.The decline in cognitive performance that occurs in AR is paralleled by a marked reduction in neurogenesis. We hypothesized that regenerative medicine is a promising approach to reverse these changes. Adult bone marrow-derived MSCs (BM-MSCs) have been reported as potential candidates for treatment of neurodegenerative disorders. They have multiple beneficial effects in the brain and it is of particular interest that them are essentially non-immunogenic even when xenotransplanted.Here, we investigated the therapeutic potential of human BM-MSCs to treat cognitive impairment in AR. Dil-labeled human BM-MSCs were intracerebroventricularly (ICV) 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.Additionally, we performed time-course studies for MSCs integration and viability in the brain and assessed a set of hippocampal cell markers.