Cholinergic Grb2-associated-binding protein 1 regulates cognitive function

Nan Nan Lu, Chao Tan, Ning He Sun, Ling Xiao Shao, Xiu Xiu Liu, Yin Ping Gao, Rong Rong Tao, Quan Jiang, Cheng Kun Wang, Ji Yun Huang, Kui Zhao, Guang Fa Wang, Zhi Rong Liu, Kohji Fukunaga, Ying Mei Lu, Feng Han

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Grb2-associated-binding protein 1 (Gab1) is a docking/scaffolding molecule known to play an important role in cell growth and survival. Here, we report that Gab1 is decreased in cholinergic neurons in Alzheimer's disease (AD) patients and in a mouse model of AD. In mice, selective ablation of Gab1 in cholinergic neurons in the medial septum impaired learning and memory and hippocampal long-term potentiation. Gab1 ablation also inhibited SK channels, leading to an increase in firing in septal cholinergic neurons. Gab1 overexpression, on the other hand, improved cognitive function and restored hippocampal CaMKII autorphosphorylation in AD mice. These results suggest that Gab1 plays an important role in the pathophysiology of AD and may represent a novel therapeutic target for diseases involving cholinergic dysfunction.

Original languageEnglish
Pages (from-to)2391-2404
Number of pages14
JournalCerebral Cortex
Volume28
Issue number7
DOIs
Publication statusPublished - 2018

Keywords

  • Cholinergic neurons
  • Cognitive dysfunction
  • Gab1
  • Hyperexcitability
  • Septo-hippocampal system

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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  • Cite this

    Lu, N. N., Tan, C., Sun, N. H., Shao, L. X., Liu, X. X., Gao, Y. P., Tao, R. R., Jiang, Q., Wang, C. K., Huang, J. Y., Zhao, K., Wang, G. F., Liu, Z. R., Fukunaga, K., Lu, Y. M., & Han, F. (2018). Cholinergic Grb2-associated-binding protein 1 regulates cognitive function. Cerebral Cortex, 28(7), 2391-2404. https://doi.org/10.1093/cercor/bhx141