Plaque associated-GFAP+ astrocytes show increasing autophagic activity in PDAPP mice, model of Alzheimer's disease.

SARAVIA F; PAVÍA P; POMILIO C; VINUESA A; GOROJOD RM; ALAIMO A; KOTLER ML; GALVÁN V; BEAUQUIS J

Berlin

Congreso; Glial XI European Meeting; 2013

Glia

Alzheimer´s disease (AD), the most common age-dependent neurodegenerative disorder, causes a chronically progressive decline in cognitive functions. There is growing evidence that glial changes are early involved in this pathology. PDAPP mouse, a well- defined model of AD, accumulates toxic soluble and deposited Abeta, derived from proteolytic processing of the amyloid precursor protein (APP) and develops AD-like synaptic deficits and cognitive impairment. On the other hand, autophagy has been associated to the neurodegenerative process, in particular with the clearance of aggregation-prone proteins like Abeta. The amyloid plaques, mainly located in cortex and hippocampus, are closely surrounded by reactive and hypertrophic GFAP+ astrocytes. The aim of this work was to evaluate the potential astrocyte autophagic activity during the progression of AD in PDAPP mice from 5 to 20 months (m) of age. LC3II/I ratio was studied by western blot. Amyloid deposit load, stained with Congo Red, exhibited a continuing rise according to age in transgenic mice. The markers GFAP and LC3 were analyzed by immunofluorescence and confocal microscopy on hippocampal sections showing an increasing colocalization that reached the top at 14 m, where 52.5 % of plaque associated GFAP cells were LC3+. At 20 m, this proportion was lower. Conversely, the subpopulation of astrocytes located far from Abeta deposits were GFAP+/LC3-, besides a decreased cell volume compared with control mice astrocytes. Additionally, the density of astroglial cells in the stratum radiatum diminished with aging (5 compared to 14 m, total GFAP+ cells, p