Correcting miR92a-vGAT-Mediated GABAergic Dysfunctions Rescues Human Tau-Induced Anxiety in Mice.

ABSTRACT: Patients with Alzheimer's disease (AD) commonly show anxiety behaviors, but the molecular mechanisms are not clear and no efficient intervention exists. Here, we found that overexpression of human wild-type, full-length tau (termed htau) in hippocampus significantly decreased the extracellular γ-aminobutyric acid (GABA) level with inhibition of γ oscillation and the evoked inhibitory postsynaptic potential (eIPSP). With tau accumulation, the mice show age-dependent anxiety behaviors. Among the factors responsible for GABA synthesis, release, uptake, and transport, we found that accumulation of htau selectively suppressed expression of the intracellular vesicular GABA transporter (vGAT). Tau accumulation increased miR92a, which targeted vGAT mRNA 3' UTR and inhibited vGAT translation. Impor

SUBMITTER: Li X 

PROVIDER: S-EPMC5363302 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature