GFAP mutation and astrocyte dysfunction lead to a neurodegenerative profile with impaired synaptic plasticity and cognitive deficits in a rat model of Alexander disease.

ABSTRACT: Alexander disease (AxD) is a rare neurological disorder caused by dominant gain-of-function mutations in the gene for glial acidic fibrillary protein (GFAP). Expression of mutant protein results in astrocyte dysfunction that ultimately leads to developmental delay, failure to thrive, and intellectual and motor impairment. The disease is typically fatal, and at present there are no preventative or effective treatments. To gain a better understanding of the link between astrocyte dysfunction and behavioral deficits in AxD we recently developed a rat model that recapitulates many of the clinical features of the disease, including failure to thrive, motor impairment, and white matter deficits. In the present study, we show that both male and female AxD model rats exhibit a neurodegenera

SUBMITTER: Berman RF 

PROVIDER: S-EPMC11936449 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature