Altered hippocampal neurogenesis in a transgenic mouse model of Alzheimer’s disease. Changes induced by long term exposure to an enriched environment.

BEAUQUIS J; GALVÁN V; ROIG P; GOROSTIZA O; DE NICOLA AF; SARAVIA F

Huerta Grande, Córdoba.

Congreso; Primera Reunión Conjunta de Neurociencias (IRCN); 2009

Sociedad Argentina de Investigación en Neurociencias - Taller Argentino de Neurociencias

Evidence from the literature suggests that cognitive stimulation can be protective in some neurodegenerative diseases, including AD. Our aim was to explore the effect of 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, and their siblings (non-tg) were housed in special cages containing tubes, nesting material, a house and toys, or in standard conditions (SC) for 3 months (5 to 8 months of life). Proliferation rates measured by Ki67 labeling in the dentate gyrus were lower in tg mice compared with controls with no effects of EE. Tg mice showed a decrease in doublecortin cells in the dentate gyrus. Survival of newborn cells was examined by administration of bromodeoxyuridine (BrdU) 21 d 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 -calculated on the basis of colocalization of BrdU labeling with the neuronal marker NeuN using confocal microscopy- were low for tg mice housed in SC but EE strongly increased this ratio, suggesting that more neurons were produced in the dentate gyrus from stimulated tg mice. Working memory was evaluated in the Y maze: spontaneous alternation was clearly improved in tg mice after EE exposure. However, no differences in numbers of Abeta plaques in CA1 were observed in tg groups. Our results suggest an important role for social, sensory and cognitive stimuli in the pathogenesis of AD.