1. Academic Validation
  2. Microglia-derived PDGFB promotes neuronal potassium currents to suppress basal sympathetic tonicity and limit hypertension

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

  • Immunity. 2022 Aug 9;55(8):1466-1482.e9. doi: 10.1016/j.immuni.2022.06.018.
Qianqian Bi 1 Chao Wang 2 Guo Cheng 1 Ningting Chen 1 Bo Wei 1 Xiaoli Liu 3 Li Li 4 Cheng Lu 1 Jian He 5 Yuancheng Weng 5 Chunyou Yin 5 Yunfan Lin 6 Shu Wan 7 Li Zhao 8 Jiaxi Xu 9 Yi Wang 10 Yan Gu 11 Xiao Z Shen 12 Peng Shi 13
Affiliations

Affiliations

  • 1 Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
  • 2 Center of Stem Cell and Regenerative Medicine and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • 3 Department of Neurology, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
  • 4 Department of Pharmacy, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310013, China.
  • 5 Department of Physiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
  • 6 Zhejiang University-University of Edinburgh Institute, Zhejiang University School of Medicine, Haining, Zhejiang 314400, China.
  • 7 Brain Center, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
  • 8 Key Laboratory for Biomedical Engineering of Ministry of Education, College of Biomedical Engineering & Instrument Science, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • 9 Department of Physiology and Pathophysiology, Xi'an Jiaotong University Health Science Center, Xi'an, Shanxi 710061, China.
  • 10 Department of Pharmacology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China.
  • 11 Center of Stem Cell and Regenerative Medicine and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Science & Brain-Machine Integration, Zhejiang University, Hangzhou, Zhejiang 310058, China. Electronic address: guyan2015@zju.edu.cn.
  • 12 Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Department of Physiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. Electronic address: shenx@zju.edu.cn.
  • 13 Department of Cardiology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China; Institute of Translational Medicine, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058, China. Electronic address: ship@zju.edu.cn.
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 neurons in the hypothalamic paraventricular nucleus (PVN) at steady state. Microglia constitutively released platelet-derived growth factor (PDGF) B, which signaled via PDGFRα on neuronal cells and promoted their expression of Kv4.3, a key subunit that conducts potassium currents. Ablation of microglia, conditional deletion of microglial PDGFB, or suppression of neuronal PDGFRα expression in the PVN elevated the excitability of pre-sympathetic neurons and sympathetic outflow, resulting in a profound autonomic dysfunction. Disruption of the PDGFBMG-Kv4.3Neuron pathway predisposed mice to develop hypertension, whereas central supplementation of exogenous PDGFB suppressed pressor response when mice were under hypertensive insult. Our results point to a non-immune action of resident microglia in maintaining the balance of sympathetic outflow, which is important in preventing cardiovascular diseases.

Keywords

Kcnd3; Kv4.3; PDGFR inhibitor; hypertension; hypothalamic paraventricular nucleus; microglia; paracrine action; platelet-derived growth factor B; potassium current; sympathetic nerve activity.

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