C.I. Fernández, A. Toledano, M.E. González, E. Alberti, L. Hidalgo, M.A. León Díaz del Guante

Background. Neurogenic events and associated behavioral improvements have been reported after housing under enrichment environment conditions (EE), demonstrating the presence of newborn cells from neurogenic niches. Previous studies have demonstrated the bone marrow stem cells (BMSC) possibilities as source of tissue in brain grafting studies. Objectives: To compare functional effects induced by EE (12 weeks, 6 hours/day) and/or hippocampal BMSC grafting (H-Graft) in an early Alzheimer´s disease rat model. Methods. BMSCs cellular suspensions were processed to allow green or blue fluorescent detection. After it, they were grafted to the hippocampus of mild cognitive-impaired aged rats (18 months old). Classical stains and BrU labeling/ counting cells were used to determine their migration and engraftment conditions. Cognitive performance was studied using the Morris Water Maze, passive avoidance and open field tests, before and after treatment (12/24 weeks). After it, animals were sacrified for morphological or neurochemical studies (aminoacid levels –Aas- and glutathione content –GSH- determinations. Results. All treated animals improved their initial cognitive status. Both, H-Graft and EE rats exhibit a recovery in the assessed cogntive domains but a relevant and chronic recovery was detected in EE + H-Graft. Similarly, GSH and AAs levels exhibit a marked and favourable modifications comparing with control groups. Results suggest , that additionally to increased of neurogenic activity, neuroprotective events took place. “Function improved” was a key criterion for evaluate the effectiveness of neurogenesis –endogenous or exogenous- associated to neurorestorative approaches. At system level and its functional expression was observed different improvements but the exact causes-consequences relationship between function and neurogenesis-niche interactions couldn’t be clarified at all. Conclusions. Brain regeneration, either with endogenous or exogenous new cells, clearly holds promise as a novel class of therapies to cognitive and neurochemical disturbances in the aged –impaired/demented brain.

Keywords (Optional): 
animal model
early Alzheimer's disease
stem cell grafting
cognitive impairment
environment enrichment