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

Kanchan Bisht, Kenneth A. Okojie, Kaushik Sharma, Dennis H. Lentferink, Yu-Yo Sun, Hong-Ru Chen, Joseph O. Uweru, Saipranusha Amancherla, Zainab Calcuttawala, Antony Brayan Campos-Salazar, Bruce Corliss, Lara Jabbour, Jordan Benderoth, Bria Friestad, William A. Mills, Brant E. Isakson, Marie-Ève Tremblay, Chia-Yi Kuan and Ukpong B. Eyo ()
Additional contact information
Kanchan Bisht: University of Virginia School of Medicine
Kenneth A. Okojie: University of Virginia School of Medicine
Kaushik Sharma: University of Virginia School of Medicine
Dennis H. Lentferink: University of Virginia School of Medicine
Yu-Yo Sun: University of Virginia School of Medicine
Hong-Ru Chen: University of Virginia School of Medicine
Joseph O. Uweru: University of Virginia School of Medicine
Saipranusha Amancherla: University of Virginia School of Medicine
Zainab Calcuttawala: University of Virginia School of Medicine
Antony Brayan Campos-Salazar: University of Virginia School of Medicine
Bruce Corliss: University of Virginia School of Medicine
Lara Jabbour: University of Virginia School of Medicine
Jordan Benderoth: University of Virginia School of Medicine
Bria Friestad: University of Virginia School of Medicine
William A. Mills: University of Virginia School of Medicine
Brant E. Isakson: University of Virginia School of Medicine
Marie-Ève Tremblay: Centre de recherche du CHU de Québec—Université Laval
Chia-Yi Kuan: University of Virginia School of Medicine
Ukpong B. Eyo: University of Virginia School of Medicine

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: 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.

Date: 2021
References: Add references at CitEc
Citations: View citations in EconPapers (5)

Downloads: (external link)
https://www.nature.com/articles/s41467-021-25590-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25590-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-25590-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().