华中科技大学同济医学院王建枝、Jie Zheng等研究人员合作发现，磷酸化tau蛋白在中间神经元中的积累通过抑制GABA能传递来损害成年海马神经发生。2020年1月23日，国际知名学术期刊《细胞—干细胞》在线发表了这一成果。

Title: Interneuron Accumulation of Phosphorylated tau Impairs Adult Hippocampal Neurogenesis by Suppressing GABAergic Transmission

Author: Jie Zheng, Hong-Lian Li, Na Tian, Fei Liu, Lu Wang, Yaling Yin, Lupeng Yue, Longyu Ma, You Wan, Jian-Zhi Wang

Issue&Volume: January 23, 2020

Abstract: Phospho-tau accumulation and adult hippocampal neurogenesis (AHN) impairment bothcontribute importantly to the cognitive decline in Alzheimer’s disease (AD), but whetherand how tau dysregulates AHN in AD remain poorly understood. Here, we found a prominentaccumulation of phosphorylated tau in GABAergic interneurons in the dentate gyrus(DG) of AD patients and mice. Specific overexpression of human tau (hTau) in miceDG interneurons induced AHN deficits but increased neural stem cell-derived astrogliosis,associating with a downregulation of GABA and hyperactivation of neighboring excitatoryneurons. Chemogenetic inhibition of excitatory neurons or pharmacologically strengtheningGABAergic tempos rescued the tau-induced AHN deficits and improved contextual cognition.These findings evidenced that intracellular accumulation of tau in GABAergic interneuronsimpairs AHN by suppressing GABAergic transmission and disinhibiting neural circuitswithin the neurogenic niche, suggesting a potential of GABAergic potentiators forpro-neurogenic or cell therapies of AD.

DOI: 10.1016/j.stem.2019.12.015

Source: https://www.cell.com/cell-stem-cell/fulltext/S1934-5909(19)30573-9#%20