RRC ID 76630
Author Kakae M, Nakajima H, Tobori S, Kawashita A, Miyanohara J, Morishima M, Nagayasu K, Nakagawa T, Shigetomi E, Koizumi S, Mori Y, Kaneko S, Shirakawa H.
Title The astrocytic TRPA1 channel mediates an intrinsic protective response to vascular cognitive impairment via LIF production.
Journal Sci Adv
Abstract Vascular cognitive impairment (VCI) refers to cognitive alterations caused by vascular disease, which is associated with various types of dementia. Because chronic cerebral hypoperfusion (CCH) induces VCI, we used bilateral common carotid artery stenosis (BCAS) mice as a CCH-induced VCI model. Transient receptor potential ankyrin 1 (TRPA1), the most redox-sensitive TRP channel, is functionally expressed in the brain. Here, we investigated the pathophysiological role of TRPA1 in CCH-induced VCI. During early-stage CCH, cognitive impairment and white matter injury were induced by BCAS in TRPA1-knockout but not wild-type mice. TRPA1 stimulation with cinnamaldehyde ameliorated BCAS-induced outcomes. RNA sequencing analysis revealed that BCAS increased leukemia inhibitory factor (LIF) in astrocytes. Moreover, hydrogen peroxide-treated TRPA1-stimulated primary astrocyte cultures expressed LIF, and culture medium derived from these cells promoted oligodendrocyte precursor cell myelination. Overall, TRPA1 in astrocytes prevents CCH-induced VCI through LIF production. Therefore, TRPA1 stimulation may be a promising therapeutic approach for VCI.
Volume 9(29)
Pages eadh0102
Published 2023-7-21
DOI 10.1126/sciadv.adh0102
PMID 37478173
PMC PMC10361588
MeSH Animals Astrocytes Brain Ischemia* / complications Cognitive Dysfunction* / complications Disease Models, Animal Leukemia Inhibitory Factor / pharmacology Mice Mice, Inbred C57BL TRPA1 Cation Channel / genetics Transient Receptor Potential Channels* White Matter*
IF 13.117
Mice RBRC04495