IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
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
Autor/es:
BEAUQUIS J; GALVÁN V; ROIG P; DE NICOLA AF; SARAVIA F
Lugar:
Baeza, España.
Reunión:
Workshop; Cell Replacement for Regeneration in the Nervous System: Lessons from Adult Neurogenesis; 2010
Institución organizadora:
Universidad Internacional de Andalucía
Resumen:
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 number of beta amyloid (Abeta) plaques in the CA1 hippocampal subfield were observed between SC and EE groups, soluble Abeta 1-40 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<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 were decreased in tg mice housed in SC. However, enriched housing 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). Our results suggest an important role for social and sensorial stimuli in the pathogenesis of AD.