Disruption of the Na+/K+-ATPase-purinergic P2X7 receptor complex in microglia promotes stress-induced anxiety

Huang，Songqiang1; Dong，Wanting2; Lin，Xiaoqian1; Xu，Kangtai3; Li，Kun3; Xiong，Siping4; Wang，Zilong3; Nie，Xiaowei5; Bian，Jin Song1

2024-03-12

10.1016/j.immuni.2024.01.018

Immunity   影响因子和分区

1074-7613

1097-4180

Na/K-ATPase (NKA) plays an important role in the central nervous system. However, little is known about its function in the microglia. Here, we found that NKAα1 forms a complex with the purinergic P2X7 receptor (P2X7R), an adenosine 5′-triphosphate (ATP)-gated ion channel, under physiological conditions. Chronic stress or treatment with lipopolysaccharide plus ATP decreased the membrane expression of NKAα1 in microglia, facilitated P2X7R function, and promoted microglia inflammatory activation via activation of the NLRP3 inflammasome. Accordingly, global deletion or conditional deletion of NKAα1 in microglia under chronic stress-induced aggravated anxiety-like behavior and neuronal hyperexcitability. DR5-12D, a monoclonal antibody that stabilizes membrane NKAα1, improved stress-induced anxiety-like behavior and ameliorated neuronal hyperexcitability and neurogenesis deficits in the ventral hippocampus of mice. Our results reveal that NKAα1 limits microglia inflammation and may provide a target for the treatment of stress-related neuroinflammation and diseases.

anxiety-like behavior ATP chronic stress DR5-12D antibody inflammation microglia activation NKAα1 P2X7R ventral hippocampus

SCI

英语

第一 ; 通讯

IMMUNOLOGY

2-s2.0-85187022996

Scopus

1.Department of Pharmacology,Joint Laboratory of Guangdong-Hong Kong Universities for Vascular Homeostasis and Diseases,School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China
2.Department of Pharmacology,School of Basic Medicine,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,Hubei,430030,China
3.Department of Neuroscience,School of Medicine,Southern University of Science and Technology,Shenzhen,Guangdong,518055,China
4.Department of Pathology,the Eighth Affiliated Hospital of Sun Yat-Sen University,Shenzhen,Guangdong,518033,China
5.Key Laboratory of Shenzhen Respiratory Disease,Shenzhen Institute of Respiratory Disease,Shenzhen People's Hospital,the First Affiliated Hospital of Southern University of Science and Technology,the Second Clinical Medical College of Jinan University,Shenzhen,Guangdong,518020,China

Huang，Songqiang,Dong，Wanting,Lin，Xiaoqian,et al. Disruption of the Na+/K+-ATPase-purinergic P2X7 receptor complex in microglia promotes stress-induced anxiety[J]. Immunity,2024,57(3):495-512.e11.

Huang，Songqiang.,Dong，Wanting.,Lin，Xiaoqian.,Xu，Kangtai.,Li，Kun.,...&Bian，Jin Song.(2024).Disruption of the Na+/K+-ATPase-purinergic P2X7 receptor complex in microglia promotes stress-induced anxiety.Immunity,57(3),495-512.e11.

Huang，Songqiang,et al."Disruption of the Na+/K+-ATPase-purinergic P2X7 receptor complex in microglia promotes stress-induced anxiety".Immunity 57.3(2024):495-512.e11.