SVCT2-mediated ascorbic acid uptake buffers stress responses via DNA hydroxymethylation reprogramming of S100 calcium-binding protein A4 gene.

ABSTRACT: Vitamin C, a key antioxidant in the central nervous system, cycles between ascorbic acid and dehydroascorbic acid under pathophysiological conditions. Clinical evidence supports that the absence of vitamin C may be linked to depressive symptoms, but much less is known about the mechanism. Herein, we show that chronic stress disrupts the expression of ascorbic acid transporter, sodium-dependent vitamin C transport 2, and induces a deficiency in endogenous ascorbic acid in the medial prefrontal cortex, leading to depressive-like behaviors by disturbing redox-dependent DNA methylation reprogramming. Attractively, ascorbic acid (100 mg/kg-1000 mg/kg, intraperitoneal injection, as bioequivalent of an intravenous drip dose of 0.48 g-4.8 g ascorbic acid per day in humans) produces rapid-acting an

SUBMITTER: Han QQ 

PROVIDER: S-EPMC9694147 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature