ENVIROMENTAL ENRICHMENT PREVENTS ASTROGLIAL PATHOLOGICAL CHANGES IN THE HIPPOCAMPUS OF APP TRANSGENIC MICE, MODEL OF ALZHEIMER?S DISEASE

BEAUQUIS J; PAVIA P; POMILIO C; VINUESA A; PODLUTSKAYA N; GALVAN V; SARAVIA F

EXPERIMENTAL NEUROLOGY

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: San Diego; Año: 2013 vol. 239 p. 28 - 37

0014-4886

Alzheimer?s disease (AD) is a neurodegenerative disease that affects neurons and glial cells and leads to dementia. Growing evidence shows that glial changes may precede neuronal alterations and behavioral impairment in the progression of the disease. The modulation of these changes could be a potential therapeutic strategy. Environmental enrichment has been classically associated to effects on neuronal morphology and function but less attention has been paid to the modulation of glia. We thus characterized astroglial changes in the hippocampus of adult PDAPP-J20 transgenic mice, a model of AD, exposed for 3 months to an enriched environment, from 5 to 8 months of age. Using confocal microscopy, three-dimensional reconstruction and Sholl analysis, we evaluated the morphology of two distinct populations of astrocytes: those associated to amyloid β plaques and those that were not. We found that plaque-associated astrocytes had increased volume and process ramification than control astrocytes. Non-plaque-associated astrocytes in PDAPP-J20 mice showed a decrease in volume and an increase in the ramification of GFAP+ processes as compared with control astrocytes. Environmental enrichment prevented these alterations and promoted a cellular morphology similar to that found in control mice. Morphological changes in non-plaque-associated astrocytes were found also at 5 months of age, before amyloid β deposition in the hippocampus. These results suggest that glial alterations have an early onset in AD pathogenesis and that the exposure to an enriched environment is an appropriate strategy to reverse them. Cellular and molecular pathways involved in this regulation could constitute potential novel therapeutic targets