Early Astrocytic atrophy in the Entorhinal Cortex of a Triple Transgenic Animal Model of Alzheimer's Disease.

摘要

Background:The Entorhinal cortex (EC) is the first brain region affected by Alzheimer’s disease (AD), which is a progressive neurodegenerative disease characterized by memory deficits and the most common cause for dementia. EC has dense connections with other cognitive areas such as neocortex and hippocampus, being fundamental for information transfer and integration. As the rest of the CNS, astrocytes, in addition to neurons, are key players not only in normal conditions, but also in pathological processes by modulating brain homeostasis and synaptic connectivityMethods:we analyzed astrocytic changes within the EC in AD by measuring the surface and volume of glial fibrillary acidic protein (GFAP), which is the major glia cytoskeleton protein. For this we used the recently developed triple transgenic mice (3xTg-AD) which mimic the spatio-temporal progression of AD at different ages (1-18 months).Results:We found a significant decrease of both astrocytic GFAP surface and volume in 3xTg-AD animals compared to non transgenic (non-TG) controls; this decrease was observed from early ages (1 month, 48.04% and 44.52% in surface and volume, respectively) and sustained throughout life time (up to 12 month, 32.50% and 32.25% in surface and volume, respectively).These changes demonstrate that from early AD stages and during its progression there is a reduced astrocytic arborisation and domain as demonstrated by their cytoskeleton alterations.Conclusions:Our results suggest that structural glial changes in EC may affect the homeostasis and thus synaptic activity and connectivity of the EC, which will result in the subsequent altered glial structure and synaptic organisation in the hippocampus; accounting therefore for the cognitive deficits of AD