Neuroprotective Effect of Different Doses of Vitamine D3 in Diabetic-Induced Alzheimer Rat Model

Background: Many studies revealed that diabetes is an independent risk factor for developing cognitive dysfunction, and Alzheimer. During diabetes, overexpression of nitric oxide, tumor necrosis factor, interleukin-6 and interleukin-1 beta could lead to Aβ accumulation and neuronal death.

Aim: To examine the neuroprotective effect of different doses of vitamin D3 against diabetic-induced cognitive dysfunction in rats. Moreover, possible underlying mechanisms were also investigated.

Methods: High-fat diet plus streptozotocin were used to induce diabetes in Westar rats. We sub-grouped the diabetic rats into six subgroups, positive control, vitamin D3 groups (100, 500 and 1000 IU/kg/day), vitamin D3 plus rivastigmine, and rivastigmine monotherapy. After the induction of diabetes, we started treatment for sixteen months. Morris water maze test was used to evaluate cognitive function, followed by estimation of beta-amyloid-42, inducible nitric oxide synthase, nitric oxide, tumor necrosis factor, interleukin-6, and interleukin-1β levels in the hippocampus by ELIZA kits.

Results: Vitamin D3 treatment significantly (p<0.05) and dose-dependently mitigated cognitive deficits observed in Morris water maze test, with significant, suppresses in beta-amyloid-42 and nitric oxide synthase pathway via attenuated hippocampal inducible nitric oxide synthase and nitric oxide overproduction (p<0.05). Moreover, vitamin D3 decreased inflammation state of diabetic rats brains by significantly lowered (p<0.05) pro-inflammatory cytokines levels including, tumor necrosis factor, interleukin-6 and interleukin-1β as an underlying mechanism for the resulted improvement.

Conclusion: The results of this research suggest that upregulation of nitric oxide synthase pathway along with the increase in pro-inflammatory cytokines is critically involved in cognitive dysfunction associated with diabetes. Vitamin D3 can ameliorate these effects and has a promising neuroprotective effect in diabetic-induced cognitive dysfunction.