ADAM17 Supports Disinhibition of Pre-sympathetic Glutamatergic Neurons Through Microglial Chemotaxis
Document Type
Article
Publication Date
8-4-2025
Publication Title
Neuroscience Bulletin
Abstract
A disintegrin and metalloprotease 17 (ADAM17) is a membrane-bound enzyme that cleaves cell-surface proteins. Here, we discovered that neuronal ADAM17-mediated signaling supports the reduction of inhibitory presynaptic inputs to the pre-sympathetic glutamatergic neural hub, located in the paraventricular nucleus of the hypothalamus (PVN), upon stimulation by angiotensin II (Ang-II). For Ang-II-induced disinhibition, targeting microglial migration had an effect similar to ADAM17 knockout in glutamatergic neurons. Ang-II promoted neuron-mediated chemotaxis of microglia via neuronal CX3CL1 and ADAM17. Inhibiting microglial chemotaxis by targeting CX3CR1 abolished the Ang-II-induced microglial displacement of GABAergic presynaptic terminals and significantly blunted Ang-II’s pressor response. Using conditional and targeted knockout models of ADAM17, an increase in the contact between pre-sympathetic neurons and reactive microglia in the PVN was demonstrated to be neuronal ADAM17-dependent during the developmental stage of salt-sensitive hypertension. Collectively, this study provides evidence that neuronal ADAM17-mediated microglial chemotaxis facilitates the disinhibition of pre-sympathetic glutamatergic tone upon hormonal stimulation.
PubMed ID
40758224
Recommended Citation
Wang, Jiawei; Qiu, Zihan; Han, Yue; Wu, Hanxue; Yuan, Miao; Liu, Yan; Wang, Huichao; Yuan, Shenglan; Gao, Dengfeng; Sun, Lina; Chen, Xingjuan; Lazartigues, Eric; Li, Fanni; Yang, Rui; and Xu, Jiaxi, "ADAM17 Supports Disinhibition of Pre-sympathetic Glutamatergic Neurons Through Microglial Chemotaxis" (2025). School of Graduate Studies Faculty Publications. 384.
https://digitalscholar.lsuhsc.edu/sogs_facpubs/384
10.1007/s12264-025-01471-8