Vitamin D3 Attenuates Type 3 Diabetic-Associated Cognitive Deficits in Rats through Regulating Neurotrophins and Enhancing Cholinergic Transmission Pathway

Objective: To examine the protective effect of Vitamin D3 against Type 3 diabetes-induced cognitive dysfunction in rats. Materials and Methods: Type 3 diabetes was induced by a high-fat diet plus streptozotocin in rats. Rats were divided into seven groups: negative control, positive control, Vitamin D3 groups (100, 500 and 1000 IU/kg/day), Vitamin D3 plus rivastigmine, and rivastigmine monotherapy. A radial arm maze test was used to assess cognitive function. Levels of acetylcholinesterase (AChE), dopamine (DA), nerve growth factor, neurotrophin-3 (NT-3), and glial cell line-derived neurotrophic factor (GDNF) in the hippocampus were estimated by the enzyme-linked immunosorbent assay kits. Results: Chronic treatment with Vitamin D3 significantly (P < 0.05) and dose dependently alleviated cognitive deficits, with enhancing cholinergic transmission pathway activity through attenuated hippocampal AChE and increased DA level (P < 0.001). Moreover, Vitamin D3 significantly increased (P < 0.001) neurotrophin levels as an underlying mechanism for the resulted improvement. Conclusion: Vitamin D3 plus rivastigmine (combined group) is better than Vitamin D (100 and 500 mg/kg/day) for improvement of AChE, DA, NT-3, and GDNF levels. Vitamin D (500 and 1000 IU/kg/day) was effective as a combined group in terms of the behavioral test.