title: Early astrocytic atrophy in the entorhinal cortex of a triple transgenic animal model of Alzheimer's disease.
abstract: The EC (entorhinal cortex) is fundamental for cognitive and mnesic functions. Thus damage to this area appears as a key element in the progression of AD (Alzheimer's disease), resulting in memory deficits arising from neuronal and synaptic alterations as well as glial malfunction. In this paper, we have performed an in-depth analysis of astroglial morphology in the EC by measuring the surface and volume of the GFAP (glial fibrillary acidic protein) profiles in a triple transgenic mouse model of AD [3xTg-AD (triple transgenic mice of AD)]. We found significant reduction in both the surface and volume of GFAP-labelled profiles in 3xTg-AD animals from very early ages (1 month) when compared with non-Tg (non-transgenic) controls (48 and 54%, reduction respectively), which was sustained for up to 12 months (33 and 45% reduction respectively). The appearance of Aβ (amyloid β-peptide) depositions at 12 months of age did not trigger astroglial hypertrophy; nor did it result in the close association of astrocytes with senile plaques. Our results suggest that the AD progressive cognitive deterioration can be associated with an early reduction of astrocytic arborization and shrinkage of the astroglial domain, which may affect synaptic connectivity within the EC and between the EC and other brain regions. In addition, the EC seems to be particularly vulnerable to AD pathology because of the absence of evident astrogliosis in response to Aβ accumulation. Thus we can consider that targeting astroglial atrophy may represent a therapeutic strategy which might slow down the progression of AD.
authors: The University of Manchester, Manchester, U.K.
authors: Chia-Yu
authors: CY
authors: Yeh
authors: Bhamini
authors: B
authors: Vadhwana
authors: Alexei
authors: A
authors: Verkhratsky
authors: José J
authors: JJ
authors: Rodríguez
mesh_terms: D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000473:pathology*; D001284:Atrophy / Q000473:pathology*; D003599:Cytoskeleton / Q000473:pathology / Q000648:ultrastructure; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000166:cytology / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D058225:Plaque, Amyloid / Q000473:pathology
chemical_list: D005904:Glial Fibrillary Acidic Protein