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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

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Abstract

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-α 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 μg/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-α 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-α 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-α (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.

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Data availability

Data is available on request.

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Funding

This work was supported by the Semnan University of Medical Sciences (Grant Number 1721).

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Authors and Affiliations

  1. Research Center of Physiology, Semnan University of Medical Sciences, Semnan, Iran

    Katayoun Sedaghat, Ramtin Naderian & Roghayeh Pakdel

  2. Department of Biochemistry, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran

    Ahmad-Reza Bandegi & Zahra Ghods

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  1. Katayoun Sedaghat
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  2. Ramtin Naderian
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Contributions

Conceptualization: KS; Methodology: KS, RN, RP, ARB and ZG; Formal analysis and investigation: KS, RN, ARB; Writing—original draft preparation: KS; Writing—review and editing: KS, ARB; Funding acquisition: KS; Resources: KS; Supervision: KS, ARB.

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Correspondence to Katayoun Sedaghat.

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All experimental procedures were performed under the approval of the Animal Care and Use Committee of Semnan University of Medical Sciences (ethic number: IR.SEMUMS.REC.1398.312).

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Sedaghat, K., Naderian, R., Pakdel, R. et al. 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. Mol Biol Rep 48, 7865–7873 (2021). https://doi.org/10.1007/s11033-021-06810-2

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