Altered hippocampal neurogenesis in a transgenic Mouse of Alzheimer´s disease (AD). Changes induced by long term exposure to an enriched environment (EE),

BEAUQUIS JUAN, GALVÁN VERÓNICA, ROIG PAULINA, GOROSTIZA OLIVIA, DE NICOLA ALEJANDRO, SARAVIA FLAVIA.

Huerta Grande, Cordoba

Workshop; IRCN First Joint Meeting of the Argentine Society for Neurosciences and the Argentine Workshop in Neuroscience; 2009

Argentine Society for Neurosciences and the Argentine Workshop in Neuroscience

ALTERED HIPPOCAMPAL NEUROGENESIS IN A TRANSGENIC MOUSE MODEL OF ALZHEIMER´S DISEASE (AD). CHANGES INDUCED BY LONG TERM EXPOSURE TO AN ENRICHED ENVIRONMENT (EE). Beauquis Juan, Galván Verónica, Roig Paulina, Gorostiza Olivia, De Nicola Alejandro, Saravia Flavia.   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 different steps of hippocampal neurogenesis in a model of AD, and their potential correlation with cognitive function.   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). Proliferation rates measured by Ki67 labeling in the dentate gyrus were significantly lower in tg mice compared with controls. EE 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<0.01 vs non-tg SC; tg EE 64±11.3 p<0.05 vs tg SC BrdU+cells). Ratios of BrdU+NeuN+/BrdU+ cells were calculated on the basis of colocalization of BrdU labeling with the neuronal marker NeuN using confocal microscopy. BrdU+NeuN+/BrdU+ ratios for tg mice housed in SC were low. EE, however, strongly increased  this ratio, suggesting that more neurons were produced in the dentate gyrus of tg mice living in an enriched environment (tg SC 0.53±0.11; tg EE 0.65±0.03p<0.01). Working memory was evaluated in the Y maze before and after EE. Spontaneous alternation was clearly improved in tg mice after EE exposure. However, no differences in numbers of Abeta plaques in CA1 were observed between SC and EE groups. Our results suggest an important role for social, sensory and cognitive stimuli in the pathogenesis of AD.