Effect of Vitamin D on Hippocampus Brain-Derived Neurotrophic Factor Level in Chronic Mild Stress Model of Depression in Rats

 Depression is one the most prevalent diseases. It is believed that the level of Brain Derived Neurotropic Factor (BDNF (protein is reduced in the hippocampus of depressed patients and animal models of depression. Antidepressants, such as serotonin reuptake inhibitors, increase BDNF levels in the brain. The present study investigated the effect of vitamin D, a possible drug for depression treatment, on BDNF levels in the hippocampus in a rat model of depression.

Methods and Materials:

 Male Wistar rats (n = 42,180 to 200g) were undergone a series of Chronic Mild Stressful (CMS) procedures on a daily bases for 3 weeks and after approval of their depression by Sucrose Preference Test (SPT), they were divided to 5 groups (n = 6); two received vitamin D treatment with either 5 or 10 microgram/kg; one, vehicle of vitamin D; one, antidepressant fluoxetine 5mg/kg, and the other group did not receive any treatment for 5 weeks. In parallel, there were 3 control non-CMS groups; one treated with vitamin D, the other with fluoxetine, and the last one without any treatment. At the end of the 8-week experiment, SPT was repeated, the hippocampus was extracted, and BDNF protein was assayed using the Enzyme Linked Immunosorbent Assay (ELISA).

 The SPT at the end of 3 weeks of CMS revealed a significant difference (P < 0.0001) in sucrose preference to water between the CMS treated (mean ± SEM, 35.18 ± 4.86) and non-CMS treated group (82.72 ± 5.73), showing the induction of depression by the CMS procedure. Treatment with vitamin D and fluoxetine improved SPT in CMS-treated rats to the level of control rats (CMS, 33.43 ± 6.26 versus vit D treated 68.78 ± 5.07, P < 0.001; CMS versus fluoxetine treated 87.19 ± 3.62, P < 0.001). The BDNF levels did not show any change in depressed versus non-depressed rats (P = 0.12). Neither vitamin D nor fluoxetine could change BDNF levels in depressed rats, though fluoxetine significantly increased protein in non-depressed rats (P < 0.0001).

 The current study showed that vitamin D did not affect BDNF protein level in the hippocampus of the depressed animals, suggesting that vitamin D could alleviate the symptoms of depression via BDNF-independent mechanisms.