Pericyte pannexin1 controls cerebral capillary diameter and supports memory function

Sandra Mai-Morente, Eugenia Isasi, Alberto Rafael, Gonzalo Budelli, Silvia Olivera-Bravo, Nathalia Vitureira and Verónica Abudara ()
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Sandra Mai-Morente: Universidad de la República
Eugenia Isasi: Universidad de la República
Alberto Rafael: Universidad de la República
Gonzalo Budelli: Universidad de la República
Silvia Olivera-Bravo: Instituto de Investigaciones Biológicas Clemente Estable (IIBCE)
Nathalia Vitureira: Universidad de la República
Verónica Abudara: Universidad de la República

Nature Communications, 2025, vol. 16, issue 1, 1-22

Abstract: 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.

Date: 2025
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DOI: 10.1038/s41467-025-61312-0

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