Effects of vanillic acid and exercise on early-life stress-induced anxiety-, depression-like behaviors and neuronal damage in rats.

Early-life stress has been closely linked to the development of various neuropsychiatric disorders, including anxiety and depression. This study investigated the protective effects of vanillic acid, exercise, and their combination on early-life stress-induced anxiety- and depression-like behaviors and neuronal damage in the maternal separation (MS) rat model. Pups from Wistar albino rats were subjected to a maternal separation protocol, whereas control pups were not. After the MS protocol, rats were randomly divided into four groups: saline, exercise, vanillic acid (VA; 100 mg/kg, oral), or a combination group. Before decapitation, behavioral tests were conducted, and tissue samples were collected for assessments. Compared with the MS group, vanillic acid reduced corticosterone levels and anxiety- and depression-like behaviors (p < 0.05 - 0.001). Compared with the MS group, oxidative damage (malondialdehyde, glutathione, myeloperoxidase), apoptotic parameters (B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax)), neuronal damage, neuroinflammation (TNF-α, IL-6), and BDNF activity were reversed in all groups (p < 0.01 - 0.001). Nuclear factor-κB (NF-κB) was suppressed in the VA and exercise groups compared with the MS group (p < 0.001), whereas no difference was observed in the combined group. These findings suggest that vanillic acid or exercise may offer a promising strategy for mitigating the harmful neurological consequences of early-life psychological stress.