Neurodegeneration, stress and strategies for recovery

BEAUQUIS J; ROIG P; GALVAN V; DE NICOLA A; SARAVIA F

Huerta Grande

Congreso; Reunion de la SAN; 2010

SAN

Long term exposure to an enriched environment induces hippocampal changes and reduces soluble abeta levels in a transgenic mouse model of alzheimer Roig Paulina 1 ,Galván Verónica 2 ,Beauquis Juan 1 ,De Nicola Alejandro F 1,3 ,Saravia Flavia 1,3 1 Instituto de Biología y Medicina Experimental (CONICET), Buenos Aires, Argentina., 2 University of Texas Health Science Center at San Antonio, USA., 3 Facultad de Medicina, Universidad de Buenos Aires, Argentina. juanbeauquis@gmail.com Our aim was to explore the effects of environmental enrichment (EE) on the neurodegenerative process in an animal model of AD. Female transgenic mice (Tg, PDAPP-J20) carrying the Swe and Ind APP mutations and their non-transgenic siblings (NTg) were housed in EE or in standard conditions (SC) for 3 months (5 to 8 months of life). Soluble AB 1-40 and 1-42 brain levels were reduced in Tg in EE compared with Tg in SC. No differences were found in the number of AB plaques in the hippocampus. In situ hybridization for BDNF mRNA showed an increase in the dentate gyrus (DG) of Tg in EE compared with Tg in SC. Cell proliferation rate (Ki67 labeling) in the DG was significantly lower in Tg, with no effect of EE. Tg mice showed a decrease in the number of doublecortin+ cells in the DG. Survival of newborn BrdU+ cells (BrdU injected 21 days before euthanasia) showed an increase in both Tg and NTg with EE. Ratio of BrdU+NeuN+/BrdU+ cells was calculated, finding a decrease in Tg mice in SC and an increase with EE. Our results indicate that survival of hippocampal neuronal progenitors is promoted by EE in mice that model AD, correlating with increased levels of BDNF and lower levels of soluble AB. This might suggest an important role for social and sensorial stimuli in the pathogenesis of AD.