Medial septum tau accumulation induces spatial memory deficit via disrupting medial septum-hippocampus cholinergic pathway.

ABSTRACT: Tau accumulation and cholinergic impairment are characteristic pathologies in Alzheimer's disease (AD). However, the causal role of tau accumulation in cholinergic lesion is elusive. Here, we observed an aberrant tau accumulation in the medial septum (MS) of 3xTg and 5xFAD mice, especially in their cholinergic neurons. Overexpressing hTau in mouse MS (MS^hTau ) for 6 months but not 3 months induced spatial memory impairment without changing object recognition and anxiety-like behavior, indicating a specific and time-dependent effect of MS-hTau accumulation on spatial cognitive functions. With increasing hTau accumulation, the MS^hTau mice showed a time-dependent cholinergic neuron loss with reduced cholinergic projections to the hippocampus. Intraperitoneal administrati

SUBMITTER: Wu D 

PROVIDER: S-EPMC8161512 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature