Capillary-associated microglia regulate vascular structure and function through PANX1-P2RY12 coupling in mice
| Autor: | Jordan Benderoth, Lara Jabbour, Ukpong B. Eyo, Marie-Ève Tremblay, Yu-Yo Sun, Kanchan Bisht, Joseph O. Uweru, Bruce A. Corliss, Kaushik Sharma, Antony Brayan Campos-Salazar, Brant E. Isakson, Hong-Ru Chen, Saipranusha Amancherla, Kenneth A. Okojie, Zainab Calcuttawala, Dennis H. Lentferink, Chia-Yi Kuan, Bria Friestad, William A. Mills |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Male
Synaptic pruning Science Cell Green Fluorescent Proteins CX3C Chemokine Receptor 1 General Physics and Astronomy Vasodilation Cell Count Nerve Tissue Proteins Neuroimaging Molecular neuroscience General Biochemistry Genetics and Molecular Biology Connexins Article Mice Immune system Genes Reporter medicine Animals Myeloid Cells Receptor Mice Knockout Multidisciplinary Microglia Chemistry Neuro-vascular interactions Brain General Chemistry Pannexin Receptors Purinergic P2Y12 Cell biology Electrodes Implanted medicine.anatomical_structure Gene Expression Regulation nervous system Cerebrovascular Circulation Female |
| Zdroj: | Nature Communications, Vol 12, Iss 1, Pp 1-13 (2021) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | 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. Microglia are involved in debris clearance and synaptic pruning, among other processes. However, their direct interaction with the brain vasculature is less clear. Here, the authors show that capillary-associated microglia (CAMs) regulate vascular tone via PANX1-P2RY12 signalling. |
| Databáze: | OpenAIRE |
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