Transient receptor potential ankyrin 1 (TRPA1) is involved in corticosterone-induced oxidative damage in BV-2 microglial cells.

The transient receptor potential ankyrin 1 (TRPA1) is a non-selective cation channel activated by a variety of stimuli, including exogenous ligands and endogenous reactive compounds. Reactive oxygen species (ROS) and inflammatory mediators significantly influence cellular effects through TRPA1 activation. Interestingly, the blockage of TRPA1 can reduce depression-like behaviors in mice. MDD is a debilitating psychiatric condition associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and hyperactivation of microglial cells. Corticosterone (CORT), a final product of the HPA axis, is a well-known regulator of both peripheral and central immune responses and plays a significant role in promoting increased neurotoxicity. Thus, the central objective of this study was to investigate whether the pro-oxidant and pro-inflammatory effects of CORT are dependent of TRPA1 in BV-2 microglial cells. Initially, the cells were exposed to different concentrations of CORT (0.05, 1, 50, and 100 μM), HC-030031, a TRPA1 antagonist (1, 30, and 100 μM), and Allyl Isothiocyanate, a TRPA1 agonist (1, 10, 30, and 100 μM) for 24 h. The highest concentrations of CORT (50 and 100 μM) induced a reduction in cell viability and an increase in the levels of nitric oxide (NO), ROS, and double-stranded DNA (dsDNA). In addition, CORT (100 μM) increased Trpa1 and Il-17 mRNA expression. The TRPA1 antagonist (HC, 1 μM) significantly prevented some of the deleterious effects induced by CORT. These findings enhance our understanding of the harmful mechanisms caused by CORT and indicate that the cytotoxic effects of CORT may, at least in part, be dependent on TRPA1.