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

First Author  Wei B Year  2024
Journal  Immunity Volume  57
Issue  9 Pages  2030-2042.e8
PubMed ID  39116878 Mgi Jnum  J:353861
Mgi Id  MGI:7714443 Doi  10.1016/j.immuni.2024.07.011
Citation  Wei B, et al. (2024) Microglia in the hypothalamic paraventricular nucleus sense hemodynamic disturbance and promote sympathetic excitation in hypertension. Immunity
abstractText  Hypertension is usually accompanied by elevated sympathetic tonicity, but how sympathetic hyperactivity is triggered is not clear. Recent advances revealed that microglia-centered neuroinflammation contributes to sympathetic excitation in hypertension. In this study, we performed a temporospatial analysis of microglia at both morphological and transcriptomic levels and found that microglia in the hypothalamic paraventricular nucleus (PVN), a sympathetic center, were early responders to hypertensive challenges. Vasculature analyses revealed that the PVN was characterized by high capillary density, thin vessel diameter, and complex vascular topology relative to other brain regions. As such, the PVN was susceptible to the penetration of ATP released from the vasculature in response to hemodynamic disturbance after blood pressure increase. Mechanistically, ATP ligation to microglial P2Y(12) receptor was responsible for microglial inflammatory activation and the eventual sympathetic overflow. Together, these findings identified a distinct vasculature pattern rendering vulnerability of PVN pre-sympathetic neurons to hypertension-associated microglia-mediated inflammatory insults.
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