Deficits in adult neurogenesis, contextual fear conditioning, and spatial learning in a Gfap mutant mouse model of Alexander disease.

[alexander disease]

Glial fibrillary acidic protein (GFAP ) is the major intermediate filament of mature astrocytes in the mammalian CNS . Dominant gain of function mutations in GFAP lead to the fatal neurodegenerative disorder , Alexander disease (AxD ), which is characterized by cytoplasmic protein aggregates known as Rosenthal fibers along with variable degrees of leukodystrophy and intellectual disability . The mechanisms by which mutant GFAP leads to these pleiotropic effects are unknown . In addition to astrocytes , GFAP is also expressed in other cell types , particularly neural stem cells that form the reservoir supporting adult neurogenesis in the hippocampal dentate gyrus and subventricular zone of the lateral ventricles . Here , we show that mouse models of AxD exhibit significant pathology in GFAP -positive radial glia-like cells in the dentate gyrus , and suffer from deficits in adult neurogenesis . In addition , they display impairments in contextual learning and spatial memory . This is the first demonstration of cognitive phenotypes in a model of primary astrocyte disease .

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Diseases presenting "alexander disease" symptom

alexander disease

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