Prefrontal parvalbumin interneurons deficits mediate early emotional dysfunction in Alzheimer's disease

被引：18

作者：

Shu, Shu ^{[1
,2
,3
,4
,5
,6
]}

Xu, Si-Yi ^{[1
,2
,7
]}

Ye, Lei ^{[1
,2
]}

LiU, Yi ^{[1
,2
,3
,4
,5
,6
]}

Cao, Xiang ^{[1
,2
,3
,4
,5
,6
]}

Jia, Jun-Qiu ^{[1
,2
]}

Bian, Hui-Jie ^{[1
,2
,8
]}

Liu, Ying ^{[1
,2
]}

Zhu, Xiao-Lei ^{[1
,2
,3
,4
,5
,6
]}

Xu, Yun ^{[1
,2
,3
,4
,5
,6
]}

机构：

[1] Nanjing Univ, Med Sch, Dept Neurol, Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China

[2] Nanjing Univ, State Key Lab Pharmaceut Biotechnol, Nanjing 210008, Jiangsu, Peoples R China

[3] Nanjing Univ, Inst Brain Sci, Nanjing 210093, Jiangsu, Peoples R China

[4] Med Sch Nanjing Univ, Jiangsu Key Lab Mol Med, Nanjing 210008, Jiangsu, Peoples R China

[5] Jiangsu Prov Stroke Ctr Diag & Therapy, Nanjing 210008, Jiangsu, Peoples R China

[6] Nanjing Neuropsychiat Clin Med Ctr, Nanjing 210008, Jiangsu, Peoples R China

[7] Jiangsu Univ, Nanjing Drum Tower Hosp Clin Coll, Zhenjiang 212013, Jiangsu, Peoples R China

[8] Nanjing Univ Chinese Med, Nanjing Drum Tower Hosp Clin Coll, Nanjing 210023, Jiangsu, Peoples R China

来源：

NEUROPSYCHOPHARMACOLOGY | 2023年 / 48卷 / 02期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

CIRCUIT DYSFUNCTION; INHIBITION; SYNAPSES; CORTEX; MOUSE; MEMORY;

D O I：

10.1038/s41386-022-01435-w

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Alzheimer's disease (AD) is the most common neurodegenerative disease and has an insidious onset. Exploring the characteristics and mechanism of the early symptoms of AD plays a critical role in the early diagnosis and intervention of AD. Here we found that depressive-like behavior and short-term spatial memory dysfunction appeared in APPswe/PS1dE9 mice (AD mice) as early as 9-11 weeks of age. Electrophysiological analysis revealed excitatory/inhibitory (E/I) imbalance in the prefrontal cortex (PFC). This E/I imbalance was induced by significant reduction in the number and activity of parvalbumin interneurons (PV+ INs) in this region. Furthermore, optogenetic and chemogenetic activation of residual PV+ INs effectively ameliorated depressive-like behavior and rescued short-term spatial memory in AD mice. These results suggest the PFC is selectively vulnerable in the early stage of AD and prefrontal PV+ INs deficits play a key role in the occurrence and development of early symptoms of AD.

引用

页码：391 / 401

页数：11