| First Author | Bi Q | Year | 2022 |
| Journal | Immunity | Volume | 55 |
| Issue | 8 | Pages | 1466-1482.e9 |
| PubMed ID | 35863346 | Mgi Jnum | J:351515 |
| Mgi Id | MGI:7329698 | Doi | 10.1016/j.immuni.2022.06.018 |
| Citation | Bi Q, et al. (2022) Microglia-derived PDGFB promotes neuronal potassium currents to suppress basal sympathetic tonicity and limit hypertension. Immunity 55(8):1466-1482.e9 |
| abstractText | 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 PDGFRalpha 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 PDGFRalpha expression in the PVN elevated the excitability of pre-sympathetic neurons and sympathetic outflow, resulting in a profound autonomic dysfunction. Disruption of the PDGFB(MG)-Kv4.3(Neuron) 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. |
