Deletion of TRPA1 Ion Channel Modulates the Central Stress Responses in a Mouse Model of Posttraumatic Stress Disorder.

Background: Posttraumatic stress disorder (PTSD) is a mental illness in which central stress-regulating regions, including locus coeruleus (LC) and paraventricular nucleus of hypothalamus (PVN), play key roles. Clonidine, a central sympatholytic drug, can inhibit LC activity and reduce PTSD-related symptoms, suggesting noradrenergic involvement. Glia-driven immune mechanisms may link LC activity to PVN responses. Since TRPA1 ion channel is implicated in both neuroinflammation and stress adaptation, we aimed to determine whether its presence modulates the function of brain structures contributing to PTSD-related alteration in central stress adaptation. Methods: Foot shock PTSD model was applied to Trpa1 wild-type (WT) and knockout (KO) mice, and outcomes were assessed four weeks later. Immunohistochemistry was used to evaluate tyrosine hydroxylase (TH) levels in the LC and glial activation in the PVN. Behavioral effects of clonidine and circulating corticosterone levels were also examined. Results: Stress increased LC/TH immunoreactivity and PVN glial activation. Trpa1 deletion exaggerated LC/TH responses but reduced PVN astrocyte activation. Clonidine increased freezing and decreased jumping (a hyperarousal marker). KO mice showed enhanced jumping and did not respond to clonidine. Corticosterone levels remained unchanged. Conclusions: TRPA1 may support stress adaptation in PTSD by regulating LC noradrenergic output and PVN neuroinflammation, independently of α(2)-adrenergic signaling.