2. Academic Validation
  3. Disruption of the Na+/K+-ATPase-purinergic P2X7 receptor complex in microglia promotes stress-induced anxiety

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

  • Immunity. 2024 Feb 16:S1074-7613(24)00044-X. doi: 10.1016/j.immuni.2024.01.018.
Songqiang Huang 1,  Wanting Dong 2,  Xiaoqian Lin 1,  Kangtai Xu 3,  Kun Li 3,  Siping Xiong 4,  Zilong Wang 3,  Xiaowei Nie 5,  Jin-Song Bian 6
Affiliations

Affiliations

  • 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 518055, Guangdong, China.
  • 2 Department of Pharmacology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China.
  • 3 Department of Neuroscience, School of Medicine, Southern University of Science and Technology, Shenzhen 518055, Guangdong, China.
  • 4 Department of Pathology, the Eighth Affiliated Hospital of Sun Yat-Sen University, Shenzhen 518033, Guangdong, 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 518020, Guangdong, China. Electronic address: nxw912@126.com.
  • 6 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 518055, Guangdong, China. Electronic address: bianjs@sustech.edu.cn.
PMID: 38395698 DOI: 10.1016/j.immuni.2024.01.018
Abstract

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.

Keywords

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

Figures
Products
Inhibitors & Agonists