南方科技大学卞劲松等研究人员合作发现，破坏小胶质细胞中的Na⁺/K⁺-ATP酶-嘌呤能P2X7受体复合物可促进应激诱发的焦虑症。这一研究成果于2024年2月22日在线发表在国际学术期刊《免疫》上。

研究人员表示，Na⁺/K⁺-ATP酶（NKA）在中枢神经系统中发挥着重要作用。然而，人们对它在小胶质细胞中的功能知之甚少。

研究人员发现NKAα1在生理条件下与嘌呤能P2X7受体（P2X7R）形成复合物，P2X7R是腺苷5′-三磷酸（ATP）门控离子通道。慢性应激或用脂多糖加ATP处理会降低小胶质细胞中NKAα1的膜表达，促进P2X7R的功能，并通过激活NLRP3炎症小体促进小胶质细胞的炎症激活。

因此，在慢性应激诱导的焦虑样行为和神经元过度兴奋性加重的情况下，在小胶质细胞中全面或有条件地缺失NKAα1。DR5-12D是一种能稳定膜NKAα1的单克隆抗体，它能改善应激诱导的焦虑样行为，并改善小鼠腹侧海马的神经元过度兴奋性和神经发生缺陷。

这些研究结果表明，NKAα1限制了小胶质细胞炎症，可能为治疗应激相关神经炎症和疾病提供了靶点。

附：英文原文

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

Author: Songqiang Huang, Wanting Dong, Xiaoqian Lin, Kangtai Xu, Kun Li, Siping Xiong, Zilong Wang, Xiaowei Nie, Jin-Song Bian

Issue&Volume: 2024-02-22

Abstract: Na+/K+-ATPase (NKA) plays an important role in the central nervous system. However, littleis known about its function in the microglia. Here, we found that NKAα1 forms a complexwith the purinergic P2X7 receptor (P2X7R), an adenosine 5′-triphosphate (ATP)-gatedion channel, under physiological conditions. Chronic stress or treatment with lipopolysaccharideplus ATP decreased the membrane expression of NKAα1 in microglia, facilitated P2X7Rfunction, and promoted microglia inflammatory activation via activation of the NLRP3inflammasome. Accordingly, global deletion or conditional deletion of NKAα1 in microgliaunder chronic stress-induced aggravated anxiety-like behavior and neuronal hyperexcitability.DR5-12D, a monoclonal antibody that stabilizes membrane NKAα1, improved stress-inducedanxiety-like behavior and ameliorated neuronal hyperexcitability and neurogenesisdeficits in the ventral hippocampus of mice. Our results reveal that NKAα1 limitsmicroglia inflammation and may provide a target for the treatment of stress-relatedneuroinflammation and diseases.

DOI: 10.1016/j.immuni.2024.01.018

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00044-X