Regulatory effect of vitamin D on pro-inflammatory cytokines and anti-oxidative enzymes dysregulations due to chronic mild stress in the rat hippocampus and prefrontal cortical area

Background Chronic stress increases the production of pro-inflammatory cytokines and oxidative stress in the brain, which underlay cognitive and psychological problems. In addition to the anti-depressants, vitamin D is known to act as an anti-inflammatory and anti-oxidative agent. This study investigates the specific effects of vitamin D in protecting hippocampus and pre-frontal cortex (PFC) against chronic mild stress (CMS)-induced activation of pro-inflammatory cytokines IL-6 and TNF-alpha and decreasing the activation of anti-oxidative enzymes super oxide dismutase (SOD) and glutathione peroxidase (GPx). Methods and results Rats were exposed to CMS for 3 weeks. Two groups of rats received vitamin D (5 and 10 mu g/kg) and another received fluoxetine (5 mg/kg) along with CMS. Control groups were not exposed to CMS, but received treatments similar to CMS groups. Serum corticosterone and IL-6, TNF-alpha and SOD and GPx levels in the hippocampus and PFC were measured at the end of three weeks. CMS significantly increased corticosterone, IL-6, TNF-alpha and decreased SOD and GPx levels (P < 0.0001) in hippocampus and PFC. Vitamin D treatment reduced corticosterone levels (P < 0.01), increased SOD (P < 0.0001) and GPx (P < 0.01) and decreased IL-6 and TNF-alpha (P < 0.0001) levels in the hippocampus and PFC compared to rats treated with vitamin D vehicle. Vitamin D-10 regulation of SOD and IL-6 levels was more effective than fluoxetine (P < 0.0001 and P < 0.01, respectively, in hippocampus). Conclusion This study suggests that vitamin D effectively protects the key regions of the brain related to cognition and affective behavior, against the inflammation and oxidative stress caused by the chronic stress.

Automated summary

This study found that vitamin D effectively protects the hippocampus and prefrontal cortex against inflammation and oxidative stress induced by chronic mild stress.