浙江大学史鹏等研究人员合作发现，下丘脑室旁核的小胶质细胞感知血流动力学扰动并在高血压中促进交感神经兴奋。相关论文于2024年8月7日在线发表在《免疫》杂志上。

研究人员对小胶质细胞进行了形态学和转录组学的时空分析，发现下丘脑室旁核（PVN）中的小胶质细胞可作为交感神经中枢，对高血压挑战的反应较早。血管分析显示，PVN的毛细血管密度高、血管直径细且血管拓扑复杂，相较于其他脑区。这使得PVN容易受到血压升高后血管释放的ATP的渗透。

机制上，ATP与小胶质细胞P2Y₁₂受体结合导致微胶质细胞的炎症激活，最终引发交感神经的过度兴奋。综上所述，这些发现确定了特定的血管模式，使得PVN中的前交感神经元对高血压相关的小胶质细胞介导的炎症损伤具有脆弱性。

据悉，高血压通常伴随着交感神经张力的升高，但交感神经过度活跃的触发机制尚不明确。近期研究揭示了以小胶质细胞为中心的神经炎症对高血压中交感神经兴奋的贡献。

附：英文原文

Title: Microglia in the hypothalamic paraventricular nucleus sense hemodynamic disturbance and promote sympathetic excitation in hypertension

Author: Bo Wei, Guo Cheng, Qianqian Bi, Cheng Lu, Qihang Sun, Li Li, Ningting Chen, Miner Hu, Haoran Lu, Xuancheng Xu, Genxiang Mao, Shu Wan, Zhechun Hu, Yan Gu, Jiaxin Zheng, Li Zhao, Xiao Z. Shen, Xiaoli Liu, Peng Shi

Issue&Volume: 2024-08-07

Abstract: Hypertension is usually accompanied by elevated sympathetic tonicity, but how sympathetichyperactivity is triggered is not clear. Recent advances revealed that microglia-centeredneuroinflammation contributes to sympathetic excitation in hypertension. In this study,we performed a temporospatial analysis of microglia at both morphological and transcriptomiclevels and found that microglia in the hypothalamic paraventricular nucleus (PVN),a sympathetic center, were early responders to hypertensive challenges. Vasculatureanalyses revealed that the PVN was characterized by high capillary density, thin vesseldiameter, and complex vascular topology relative to other brain regions. As such,the PVN was susceptible to the penetration of ATP released from the vasculature inresponse to hemodynamic disturbance after blood pressure increase. Mechanistically,ATP ligation to microglial P2Y12 receptor was responsible for microglial inflammatory activation and the eventualsympathetic overflow. Together, these findings identified a distinct vasculature patternrendering vulnerability of PVN pre-sympathetic neurons to hypertension-associatedmicroglia-mediated inflammatory insults.

DOI: 10.1016/j.immuni.2024.07.011

Source: https://www.cell.com/immunity/abstract/S1074-7613(24)00360-1