Depression is considered as a mood disorder that is characterized by change in mood, lack of confidence and lack of interest in surroundings. The present study was planned to investigate the antidepressant activity of vitamin D plus calcium in combinationagainst depression induced in the experimental model in attempt to clarify its mode of action.This study was conducted on 40 adult male albino rats (3 months old) divided into 4 groups n=10 Gp.(1) negative control group, Gp.(2) reserpinized group ( positive control group) received reserpine in a dose of 0.1 mg/kg b.wt., Gp.(3) reserpinized group treated with low dose of vitamin D(6 mg/kg b.wt) plus calcium (13.5 mg /rat/day) and Gp.(4) reserpinized group treated with high dose of vitamin D (12 mg/kg b.wt) plus calcium (27 mg /rat/day) . Brain neurotransmitters (serotonin and dopamine) contents, the value of brain proinflammatory cytokine (TNF-α), the content of brain derived neutrophic factor (BDNF) and the level of the antiapoptic mediator (Bcl-2) as well as survivin expression and the histological examination in the brain tissue were carried out. In comparison with the negative control group, the reserpinized group recorded significant decrease in brain serotonin and dopamine contents and significant increase in the brain content of TNF-α . Moreover, significant decrease in brain BDNF and Bcl-2 contents were detected in the reserpinized group compared with the negative control group. Histological examination of brain tissue sections of rats in the reserpinized group showed neuronal damage and shrinkage. The basophilic neurons showed core pyknosis in cerebrum. Also, dark neurons of the hippocampus and marked necrosis of the pyramidal neurons were noticed. Immunohistochemical examination of brain tissue using antibody against survivin showed weak positive reaction indicating low expression level of survivin in the brain of rats in the reserpinized group with respect to the negative control group. On the other hand, treatment of the reserpinized groups with either low or high dose of vitamin D plus calcium resulted in remarkable improvement in the biochemical parameters, immunohistocchemical and histological examination in a dose dependent manner. In conclusion, the present work provides a clear evidence for the antidepressant effect of vitamin D plus calcium through activation of serotoninergic and dopaminergic system, reduced levels of ACTH and corticosterone, inhibition of proinflammatory cytokine, promotion of neurotrophic factor and upregulation of antiapoptic markers in the brain.
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