| First Author | Huang S | Year | 2024 |
| Journal | Immunity | Volume | 57 |
| Issue | 3 | Pages | 495-512.e11 |
| PubMed ID | 38395698 | Mgi Jnum | J:358316 |
| Mgi Id | MGI:7614049 | Doi | 10.1016/j.immuni.2024.01.018 |
| Citation | Huang S, et al. (2024) Disruption of the Na(+)/K(+)-ATPase-purinergic P2X7 receptor complex in microglia promotes stress-induced anxiety. Immunity 57(3):495-512.e11 |
| abstractText | 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 NKAalpha1 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 NKAalpha1 in microglia, facilitated P2X7R function, and promoted microglia inflammatory activation via activation of the NLRP3 inflammasome. Accordingly, global deletion or conditional deletion of NKAalpha1 in microglia under chronic stress-induced aggravated anxiety-like behavior and neuronal hyperexcitability. DR5-12D, a monoclonal antibody that stabilizes membrane NKAalpha1, improved stress-induced anxiety-like behavior and ameliorated neuronal hyperexcitability and neurogenesis deficits in the ventral hippocampus of mice. Our results reveal that NKAalpha1 limits microglia inflammation and may provide a target for the treatment of stress-related neuroinflammation and diseases. |
