Chemogenetic Pericyte Activation Reveals Broad Contractile Ability and Limbic Vulnerability to Capillary Flow Deficits
Year: 2026
Type: preprint
Abstract: ABSTRACT Capillary pericytes contact most of the brain’s microvasculature. Yet, their influence on blood flow remains incompletely understood both locally in capillary networks and across brain regions. Here, we sparsely expressed the chemogenetic actuator Gq-DREADD in mouse brain pericytes to stochastically probe their contractility and influence on tissue perfusion and oxygenation. Chemogenetic stimulation induced robust contraction of pericytes over minutes, including those with thin processes on capillary segments proximal to venules, indicating control of vascular tone across the entire capillary bed. Pericyte contraction combined circumferential compression with longitudinal tension applied through thin processes, resulting in vasoconstriction and hypoperfusion. Histology revealed hypoxic microdomains induced by sparse pericyte contraction across the brain, and enriched hypoxia in limbic structures including the amygdala and hippocampus. These microscale perfusion deficits were undetectable by arterial spin labeling MRI. Our findings reveal the in vivo mechanics of pericyte contraction and identify limbic system vulnerability to capillary flow impairment.
Institutions: Seattle Children's Research Institute, University of Washington, National University of Natural Medicine, Oregon Health & Science University, University of Colorado Anschutz, Norcliffe Foundation, Cleveland Clinic, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, University of Southern California
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
Awards: The role of ATP13A5 ATPase in determining blood-brain pericyte functions, Pericyte-neuronal crosstalk in health and Alzheimer's Disease, Pericyte structural plasticity and cerebrovascular health, A TIMEM252-dependent Microvascular Endophenotype in Alzheimer’s Disease, Brain Drain: In Vivo Optical Interrogation of Venular Function in Gray and White Matter, Chemogenetic Mouse Models for Cerebral Hypoperfusion and VCID, Pericyte control of capillary perfusion in the Alzheimer's disease brain, Probing the heterogeneity of brain pericytes using new genetic tools, A TIMEM252-dependent Microvascular Endophenotype in Alzheimer’s Disease
OpenAlex ID: W7154359339