Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice.

TitleCapillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice.
Publication TypeJournal Article
Year of Publication2021
AuteursBisht, K, Okojie, KA, Sharma, K, Lentferink, DH, Sun, Y-Y, Chen, H-R, Uweru, JO, Amancherla, S, Calcuttawala, Z, Campos-Salazar, ABrayan, Corliss, B, Jabbour, L, Benderoth, J, Friestad, B, Mills, WA, Isakson, BE, Tremblay, M-È, Kuan, C-Y, Eyo, UB
JournalNat Commun
Volume12
Issue1
Pagination5289
Date Published2021 09 06
ISSN2041-1723
KeywordsAnimals, Brain, Cell Count, Cerebrovascular Circulation, Connexins, CX3C Chemokine Receptor 1, Electrodes, Implanted, Female, Gene Expression Regulation, Genes, Reporter, Green Fluorescent Proteins, Male, Mice, Mice, Knockout, Microglia, Myeloid Cells, Nerve Tissue Proteins, Neuroimaging, Receptors, Purinergic P2Y12, Vasodilation
Abstract

Microglia are brain-resident immune cells with a repertoire of functions in the brain. However, the extent of their interactions with the vasculature and potential regulation of vascular physiology has been insufficiently explored. Here, we document interactions between ramified CX3CR1 myeloid cell somata and brain capillaries. We confirm that these cells are bona fide microglia by molecular, morphological and ultrastructural approaches. Then, we give a detailed spatio-temporal characterization of these capillary-associated microglia (CAMs) comparing them with parenchymal microglia (PCMs) in their morphological activities including during microglial depletion and repopulation. Molecularly, we identify P2RY12 receptors as a regulator of CAM interactions under the control of released purines from pannexin 1 (PANX1) channels. Furthermore, microglial elimination triggered capillary dilation, blood flow increase, and impaired vasodilation that were recapitulated in P2RY12 and PANX1 mice suggesting purines released through PANX1 channels play important roles in activating microglial P2RY12 receptors to regulate neurovascular structure and function.

DOI10.1038/s41467-021-25590-8
Alternate JournalNat Commun
PubMed ID34489419
PubMed Central IDPMC8421455
Grant ListP01 HL120840 / HL / NHLBI NIH HHS / United States
R01 NS122782 / NS / NINDS NIH HHS / United States
R21 NS119727 / NS / NINDS NIH HHS / United States
R01 HL137112 / HL / NHLBI NIH HHS / United States
T32 HL007284 / HL / NHLBI NIH HHS / United States