Astroglial changes in the hippocampus of APP transgenic mice. Effects of environmental enrichment.

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

Florencia

Congreso; VIII Congress IBRO Neurosciences; 2011

IBRO

Previous publications suggest that environmental stimulation plays a protecting role in the pathogenesis of Alzheimer´s disease (AD). Our aim was to explore the effects of environmental enrichment (EE) on the neurodegenerative process in an animal model of AD, focusing on the astroglial alterations found in the hippocampus. Using this model we have previously found a decrese in hippocampal adult neurogenesis and a reversion after the exposure to EE. Female transgenic mice (Tg, PDAPP-J20) carrying the Swe and Ind APP mutations and their non-transgenic siblings (NTg) were housed in EE or in standard conditions (SC) for 3 months (5 to 8 months of life). Soluble amyloid Beta (AB) peptides 1-40 and 1-42 brain levels were reduced in Tg in EE compared with Tg in SC. Environmental enrichment had no significant effect on the the number of AB plaques in the hippocampus. Using immunohistochemistry for glial fibrillary acidic protein (GFAP) we found a diminished density of astrocytes in the CA1 field in Tg mice and an increase after EE. Double immunofluorescence for AB and GFAP, and confocal microscopy were used for measuring the volume of GFAP-positive astrocytes, dividing them into 2 populations: plaque associated (PA) and non-plaque associated (NPA) astrocytes. The analysis revealed that PA astrocytes were larger than control astrocytes, suggesting an increased reactivity, with no effect of EE. Interestingly, NPA astrocytes of Tg animals had a decreased volume when compared with astrocytes from control animals and EE was able to increase the volume to control levels. Our results indicate that in this animal model, astroglial atrophy is present in the hippocampus and this could possibly underlie the neuronal alterations that have previously been described. Environmental enrichment was shown to have an effect on the studied astroglial cells. This might suggest an important role for social and sensorial stimuli in the pathogenesis of AD, modulating not only neuronal but also astroglial populations.