Pericyte pannexin1 controls cerebral capillary diameter and supports memory function
Abstract In the blood-brain-barrier, contractile pericytes fine-tune the capillary resistance and blood supply to meet neuro-metabolic demands; molecular players governing these functions remain unclear. Here we show that mice cerebral pericytes express functional pannexin1 (Panx1) channels, which d...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-61312-0 |
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| author | Sandra Mai-Morente Eugenia Isasi Alberto Rafael Gonzalo Budelli Silvia Olivera-Bravo Nathalia Vitureira Verónica Abudara |
| author_facet | Sandra Mai-Morente Eugenia Isasi Alberto Rafael Gonzalo Budelli Silvia Olivera-Bravo Nathalia Vitureira Verónica Abudara |
| author_sort | Sandra Mai-Morente |
| collection | DOAJ |
| description | Abstract In the blood-brain-barrier, contractile pericytes fine-tune the capillary resistance and blood supply to meet neuro-metabolic demands; molecular players governing these functions remain unclear. Here we show that mice cerebral pericytes express functional pannexin1 (Panx1) channels, which drive efflux of ATP, a key activator of pericyte contractility. In hippocampal slices, pericyte Panx1 mediates capillary diameter changes in response to extracellular ATP fluctuations and glutamatergic synaptic transmission, known to contribute functional hyperaemia. Pharmacological inhibition of Panx1 in mice induces capillary widening in the cortex and hippocampus. Genetic deletion of pericyte Panx1 disrupts learning-evoked capillary dilation and memory performance. Mechanistically, glutamatergic NMDA/AMPA and purinergic P2X7/P2Y6 receptors modulate pericyte Panx1 activity, which ultimately adjusts ATP release, pericyte Ca2+ signalling and capillary dynamics. Our study unveils pericyte Panx1 as a physiological regulator of cerebral capillary diameter, which sustains brain function and serves as a potential therapeutic target for cerebrovascular cognitive disorders. |
| format | Article |
| id | doaj-art-2f3bbbe7dccd4ffe9f0655ee282f5be6 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-2f3bbbe7dccd4ffe9f0655ee282f5be62025-08-20T04:01:41ZengNature PortfolioNature Communications2041-17232025-07-0116112210.1038/s41467-025-61312-0Pericyte pannexin1 controls cerebral capillary diameter and supports memory functionSandra Mai-Morente0Eugenia Isasi1Alberto Rafael2Gonzalo Budelli3Silvia Olivera-Bravo4Nathalia Vitureira5Verónica Abudara6Departamento de Fisiología, Facultad de Medicina, Universidad de la RepúblicaDepartamento de Histología y Embriología, Facultad de Medicina, Universidad de la RepúblicaDepartamento de Fisiología, Facultad de Medicina, Universidad de la RepúblicaDepartamento de Biofísica, Facultad de Medicina, Universidad de la RepúblicaDepartamento de Neurobiología y Neuropatología, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE)Departamento de Fisiología, Facultad de Medicina, Universidad de la RepúblicaDepartamento de Fisiología, Facultad de Medicina, Universidad de la RepúblicaAbstract In the blood-brain-barrier, contractile pericytes fine-tune the capillary resistance and blood supply to meet neuro-metabolic demands; molecular players governing these functions remain unclear. Here we show that mice cerebral pericytes express functional pannexin1 (Panx1) channels, which drive efflux of ATP, a key activator of pericyte contractility. In hippocampal slices, pericyte Panx1 mediates capillary diameter changes in response to extracellular ATP fluctuations and glutamatergic synaptic transmission, known to contribute functional hyperaemia. Pharmacological inhibition of Panx1 in mice induces capillary widening in the cortex and hippocampus. Genetic deletion of pericyte Panx1 disrupts learning-evoked capillary dilation and memory performance. Mechanistically, glutamatergic NMDA/AMPA and purinergic P2X7/P2Y6 receptors modulate pericyte Panx1 activity, which ultimately adjusts ATP release, pericyte Ca2+ signalling and capillary dynamics. Our study unveils pericyte Panx1 as a physiological regulator of cerebral capillary diameter, which sustains brain function and serves as a potential therapeutic target for cerebrovascular cognitive disorders.https://doi.org/10.1038/s41467-025-61312-0 |
| spellingShingle | Sandra Mai-Morente Eugenia Isasi Alberto Rafael Gonzalo Budelli Silvia Olivera-Bravo Nathalia Vitureira Verónica Abudara Pericyte pannexin1 controls cerebral capillary diameter and supports memory function Nature Communications |
| title | Pericyte pannexin1 controls cerebral capillary diameter and supports memory function |
| title_full | Pericyte pannexin1 controls cerebral capillary diameter and supports memory function |
| title_fullStr | Pericyte pannexin1 controls cerebral capillary diameter and supports memory function |
| title_full_unstemmed | Pericyte pannexin1 controls cerebral capillary diameter and supports memory function |
| title_short | Pericyte pannexin1 controls cerebral capillary diameter and supports memory function |
| title_sort | pericyte pannexin1 controls cerebral capillary diameter and supports memory function |
| url | https://doi.org/10.1038/s41467-025-61312-0 |
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