Cholinergic Grb2-Associated-Binding Protein 1 Regulates Cognitive Function

被引：13

作者：

Lu, Nan-Nan ^{[1
]}

Tan, Chao ^{[1
]}

Sun, Ning-He ^{[1
]}

Shao, Ling-Xiao ^{[1
]}

Liu, Xiu-Xiu ^{[1
,2
]}

Gao, Yin-Ping ^{[1
,2
]}

Tao, Rong-Rong ^{[1
]}

Jiang, Quan ^{[1
]}

Wang, Cheng-Kun ^{[1
]}

Huang, Ji-Yun ^{[1
]}

Zhao, Kui ^{[3
]}

Wang, Guang-Fa ^{[3
]}

Liu, Zhi-Rong ^{[4
]}

Fukunaga, Kohji ^{[5
]}

Lu, Ying-Mei ^{[2
,6
]}

Han, Feng ^{[1
]}

机构：

[1] Zhejiang Univ, Inst Pharmacol & Toxicol, Coll Pharmaceut Sci, 866 Yu Hang Tang Rd, Hangzhou 310058, Zhejiang, Peoples R China

[2] Zhejiang Univ City Coll, Sch Med, Hangzhou 310015, Zhejiang, Peoples R China

[3] Zhejiang Univ, Affiliated Hosp 1, Sch Med, Dept PET Ctr, Hangzhou 310006, Zhejiang, Peoples R China

[4] Zhejiang Univ, Sch Med, Affiliated Hosp 2, Dept Neurol, Hangzhou 310009, Zhejiang, Peoples R China

[5] Tohoku Univ, Grad Sch Pharmaceut Sci, Dept Pharmacol, Aoba Ku, Sendai, Miyagi 9808578, Japan

[6] Zhejiang Univ, Sch Med, Dept Neurobiol, Key Lab Med Neurobiol,Minist Hlth China, Hangzhou 310058, Zhejiang, Peoples R China

来源：

CEREBRAL CORTEX | 2018年 / 28卷 / 07期

关键词：

cholinergic neurons; cognitive dysfunction; Gab1; hyperexcitability; septo-hippocampal system; HIPPOCAMPAL SYNAPTIC PLASTICITY; LONG-TERM POTENTIATION; KINASE-II; BASAL FOREBRAIN; SK CHANNELS; ALZHEIMERS-DISEASE; PREFRONTAL CORTEX; DENDRITIC SPINES; RAT-BRAIN; IN-VIVO;

D O I：

10.1093/cercor/bhx141

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：2391 / 2404

页数：14

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