Brain pericytes are an oxidative stress-sensitive cell population damaged through ROS-1 dependent TRPA1 activation.
- 1University of British Columbia
Abstract
Oxidative stress is a pathological process driven by an imbalance between the production and clearance of reactive oxygen species (ROS). It is a hallmark of numerous brain disorders, driving neuroinflammation, blood-brain barrier (BBB) disruption, and neurodegeneration. Here, we used two-photon microscopy in rodent brain slices to evaluate cell-type vulnerability to oxidative stress. We identified a microvascular cell population displaying pronounced sensitivity to H2O2 and thiol oxidation. These Pdgfr-{beta} expressing cells were identified as pericytes and perivascular fibroblasts. Because pericytes regulate capillary perfusion and BBB integrity, we examined mechanisms driving their injury. Pericyte damage was independent of apoptosis or necroptosis, but required Ca2+ influx. While blocking voltage-gated Ca2+, TRPC, Orai channels was ineffective, inhibitors of TRPA1 channels reduced pericyte damage. Immunostaining and western blotting showed TRPA1 associated with brain capillaries and pericytes. Functionally, TRPA1 regulated uptake of the pericyte-selective marker NeuroTrace, whereas pericyte GCaMP6f imaging demonstrated that TRPA1 was not the primary driver of cytosolic Ca2+ elevations during oxidative stress. These findings establish pericytes as vulnerable targets of oxidative stress and implicate TRPA1 as a mediator of pericyte structural degeneration. This sensitivity to oxidative stress, mediated by ROS-TRPA1 coupling, could contribute to the pericyte stress and degeneration observed in brain pathology.
Related
- The Oxidative Stress-Sensitive Ca²⁺ Channel, TRPM2, Contributes to Diabetes Progression Accompanied by ER Stress
- Early Insulin Signaling Defects and Oxidative Stress Kinase Activation Precede Tau Pathology in PS19 Tau Transgenic Mice
- Rv2061c, a Putative F420-Dependent Oxidoreductase, is Required for Tolerance to Malachite Green and Other Antimicrobials and Oxidative Stress Protection in Mycobacterium tuberculosis
- Selective activation of tetrodotoxin-sensitive sodium channels by AaH-II drives arrhythmogenic late Na+ current in the heart
- Activation of TLR4 promotes oxidative inflammation via NADPH oxidase signaling in platelets of subjects with autism spectrum disorder.
BibTeX
@misc{groten2026brain,
title = {{Brain pericytes are an oxidative stress-sensitive cell population damaged through ROS-1 dependent TRPA1 activation.}},
author = {C. J. Groten and J. Kwan and J. Groening and M. Belleville and N. Weilinger and Y. Bai and S. Wendt and Z. Kortje and F. Olarinde and I. Chung and H. B. Choi and L.-P. Bernier and R. Rungta and B. A. MacVicar},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.19.760199},
url = {https://www.biorxiv.org/content/10.64898/2026.10.19.760199v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Brain pericytes are an oxidative stress-sensitive cell population damaged through ROS-1 dependent TRPA1 activation.
AU - C. J. Groten
AU - J. Kwan
AU - J. Groening
AU - M. Belleville
AU - N. Weilinger
AU - Y. Bai
AU - S. Wendt
AU - Z. Kortje
AU - F. Olarinde
AU - I. Chung
AU - H. B. Choi
AU - L.-P. Bernier
AU - R. Rungta
AU - B. A. MacVicar
PY - 2026
DA - 2026/10/19
PB - bioRxiv
DO - 10.64898/2026.10.19.760199
UR - https://www.biorxiv.org/content/10.64898/2026.10.19.760199v1
AB - Oxidative stress is a pathological process driven by an imbalance between the production and clearance of reactive oxygen species (ROS). It is a hallmark of numerous brain disorders, driving neuroinflammation, blood-brain barrier (BBB) disruption, and neurodegeneration. Here, we used two-photon microscopy in rodent brain slices to evaluate cell-type vulnerability to oxidative stress. We identified a microvascular cell population displaying pronounced sensitivity to H2O2 and thiol oxidation. These Pdgfr-{beta} expressing cells were identified as pericytes and perivascular fibroblasts. Because pericytes regulate capillary perfusion and BBB integrity, we examined mechanisms driving their injury. Pericyte damage was independent of apoptosis or necroptosis, but required Ca2+ influx. While blocking voltage-gated Ca2+, TRPC, Orai channels was ineffective, inhibitors of TRPA1 channels reduced pericyte damage. Immunostaining and western blotting showed TRPA1 associated with brain capillaries and pericytes. Functionally, TRPA1 regulated uptake of the pericyte-selective marker NeuroTrace, whereas pericyte GCaMP6f imaging demonstrated that TRPA1 was not the primary driver of cytosolic Ca2+ elevations during oxidative stress. These findings establish pericytes as vulnerable targets of oxidative stress and implicate TRPA1 as a mediator of pericyte structural degeneration. This sensitivity to oxidative stress, mediated by ROS-TRPA1 coupling, could contribute to the pericyte stress and degeneration observed in brain pathology.
ER -