浙江大学医学院史鹏研究组发现小胶质细胞来源的PDGFB促进神经元钾电流抑制基础交感神经张力和限制高血压。相关论文于2022年7月20日发表于国际顶尖学术期刊《免疫》杂志上。

他们发现小胶质细胞在稳定状态下阻止了下丘脑室旁核 (PVN) 中前交感神经神经元的过度激活。小胶质细胞组成型释放血小板来源生长因子 (PDGF) B，其通过神经元细胞上的 PDGFRα 发出信号，并促进其表达 Kv4.3，Kv4.3 是传导钾电流的关键亚基。小胶质细胞的消融、小胶质细胞 PDGFB 的条件性缺失或 PVN 中神经元 PDGFRα 表达的抑制会提高前交感神经元的兴奋性和交感神经外流，从而导致严重的自主神经功能障碍。

PDGFBMG-Kv4.3神经元通路的破坏使小鼠易患高血压，而外源性PDGFB的中枢补充抑制了小鼠在高血压损伤时的升压反应。他们的结果表明常驻小胶质细胞在维持交感神经外流平衡方面的非免疫作用，即对预防心血管疾病很重要。

据悉，尽管许多研究已经解决了影响神经元活动的调节回路，但决定神经元兴奋性的局部非突触机制仍不清楚。

附：英文原文

Title: Microglia-derived PDGFB promotes neuronal potassium currents to suppress basal sympathetic tonicity and limit hypertension

Author: Qianqian Bi, Chao Wang, Guo Cheng, Ningting Chen, Bo Wei, Xiaoli Liu, Li Li, Cheng Lu, Jian He, Yuancheng Weng, Chunyou Yin, Yunfan Lin, Shu Wan, Li Zhao, Jiaxi Xu, Yi Wang, Yan Gu, Xiao Z. Shen, Peng Shi

Issue&Volume: 2022-07-20

Abstract: Although many studies have addressed the regulatory circuits affecting neuronal activities,local non-synaptic mechanisms that determine neuronal excitability remain unclear.Here, we found that microglia prevented overactivation of pre-sympathetic neuronsin the hypothalamic paraventricular nucleus (PVN) at steady state. Microglia constitutivelyreleased platelet-derived growth factor (PDGF) B, which signaled via PDGFRα on neuronalcells and promoted their expression of Kv4.3, a key subunit that conducts potassiumcurrents. Ablation of microglia, conditional deletion of microglial PDGFB, or suppressionof neuronal PDGFRα expression in the PVN elevated the excitability of pre-sympatheticneurons and sympathetic outflow, resulting in a profound autonomic dysfunction. Disruptionof the PDGFBMG-Kv4.3Neuron pathway predisposed mice to develop hypertension, whereas central supplementationof exogenous PDGFB suppressed pressor response when mice were under hypertensive insult.Our results point to a non-immune action of resident microglia in maintaining thebalance of sympathetic outflow, which is important in preventing cardiovascular diseases.

DOI: 10.1016/j.immuni.2022.06.018

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00291-6