LONG TERM EXPOSURE TO AN ENRICHED ENVIRONMENT (EE) INDUCES HIPPOCAMPAL CHANGES AND REDUCES SOLUBLE ABETA LEVELS IN A TRANSGENIC MOUSE MODEL OF ALZHEIMER´S DISEASE (AD).

BEAUQUIS J; GALVAN V; ROIG,P; DE NICOLA, AF; SARAVIA, F

Baeza

Workshop; Neuroscience Workshop; 2010

LONG TERM EXPOSURE TO AN ENRICHED ENVIRONMENT (EE) INDUCES HIPPOCAMPAL CHANGES AND REDUCES SOLUBLE ABETA LEVELS IN A TRANSGENIC MOUSE MODEL OF ALZHEIMER´S DISEASE (AD). Beauquis Juan (1), Galván Verónica (2), Roig Paulina (1), De Nicola Alejandro F (1,3), Saravia Flavia (1,3) (fsaravia@dna.uba.ar). 1=Institute of Biology and Experimental Medicine, National Research Council (CONICET) Argentina. 2= Department of Physiology, Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, USA. 3=Faculty of Medicine, University of Buenos Aires, Argentina. Evidence from the literature suggests that cognitive stimulation can be protective in some neurodegenerative diseases, including AD. The aim of the study was to explore the effect of long-term environmental enrichment on the neurodegenerative process in an animal model of AD. Female transgenic mice (tg) carrying the Swedish and Indiana Familial AD-associated mutations in the amyloid precursor protein (APP) and their siblings (non-tg) were housed in special cages containing plastic tubes, nesting material as well as a house and toys, or in standard conditions (SC) for 3 months (from 5 to 8 months of life). Even if no differences in the numbers of beta amyloid (Abeta) plaques in the CA1 hippocampal subfield were observed between SC and EE groups, soluble Abeta1-40 and 1-42 levels measured in brain homogenates were drastically reduced in tg EE. In situ hybridization for BDNF mRNA in the granular cell layer area in the dentate gyrus showed an enhancement of the expression of this neurotrophin in tg mice exposed to EE compared with SC. Concerning neurogenesis, proliferation rates measured by Ki67 labeling in the dentate gyrus were significantly lower in tg mice compared with controls. Environmental enrichment induced no changes in any experimental group. Tg mice showed a clear decrease in doublecortin + (DCX) cells in the dentate gyrus. No significant differences in the number of DCX+ cells were found in tg mice after EE. Survival of newborn cells was examined by administration of bromodeoxyuridine (BrdU) 21 days before euthanasia. EE induced a marked increase in BrdU+ cells in both groups (non-tg SC 59.8±11.4; tg SC 21.3±7.05; non-tg EE 135.2±16.9 p