Concomitant astroglial atrophy and astrogliosis in a triple transgenic animal model of Alzheimer's disease

Abstract

Astrocytes are fundamental for brain homeostasis and are at the fulcrum of neurological diseases including Alzheimer's disease (AD). Here, we monitored changes in astroglia morphology throughout the age-dependent progression of AD. We used an immunohistochemical approach that allows us to determine the domain of glial cytoskeleton, by measuring the surface, volume, and the relationship between astrocytes and neuritic plaques. We investigated astroglia in the hippocampus of a triple transgenic mouse model of AD (3xTg-AD) that mimics the progression of the human disease. The numerical density of astrocytes is affected neither by AD nor by age. We found reduction of surface and volume of GFAP profiles from early ages (6 months; 43.84 and 52.76%, respectively), persisting at 12 (40.73 and 45.39%) and 18 months (64.80 and 71.95%) in the dentate gyrus (DG) of 3xTg-AD, whereas in CA1 it appears at 18 months (29.42 and 32.74%). This cytoskeleton atrophy is accompanied by a significant reduction of glial somata volume in DG at 12 and 18 months (40.46 and 75.55%, respectively), whereas in CA1 it is significant at 18 months (42.81%). However, while astroglial atrophy appears as a generalized process, astrocytes surrounding plaques are clearly hypertrophic as revealed by increased surface (48.06%; 66.66%), and volume (57.10%; 71.06%) of GFAP profiles in DG and CA1, respectively, at 18 months. We suggest differential effects of AD on astroglial populations depending on their association with plaques accounting for the progressive disruption of neural networks connectivity and neurotransmitters imbalance which underlie mnesic and cognitive impairments observed in AD.