Investigation of minocycline treatment on behavioral and cognitive dysfunction in diabetic mice

Aim: In the present study, it was aimed to investigate the effects of minocycline and its combination with metformin on depression, anxiety and cognitive disorders emerging in type 2 diabetes mice model and the possible mechanisms inducing these effects. Material and Method: Firstly, type 2 diabetes model was induced by i.p. injection of 50 mg/kg of Streptozotocin for 5 days and using a high fat diet in mice. The assessment of diabetes model in mice was performed by controlling weekly weight alterations and monitoring fasting blood glucose levels in a regular base. Besides these, blood HbA1c levels were also measured at the end of the experiments. The behavioral parameters were evaluated by using open field, novel object recognition, modified elevated plus maze, elevated plus maze, passive avoidance, forced swimming, and hot plate tests. Malondialdehyde levels were measured for the assessment of lipid peroxidation in brain tissues. Moreover, western blotting method was performed for measurement of TNF-α, IL-6, BDNF and iba-1 expressions. Iba-1 expressions and histopathological assessment were practiced in brain sections. Results: Depression-like effects, anxiety and cognitive disorders were observed in diabetic groups (p<0.05). Minocycline and its combination with metformin had similar anti-depressant and anxiolytic effects as fluoxetine group (p<0.05). Also, it was observed that minocycline and its combination with metformin reversed spatial learning-memory impairments like the piracetam group (p<0.05). In the diabetic group, MDA levels and TNF-a, IL-6, iba-1 expression levels increased, BDNF expression levels decreased. Minocycline and its combination with metformin reversed all these parameters. Conclusion: The results of this study demonstrated minocycline has rapid and potent antidepressant-like effects. Besides that, minocycline alleviated increased anxiety and cognitive deficits in diabetic mice. Its combination with metformin has similar efficacy. In this study, it was shown that oxidation, neurodegeneration, inflammation, and microglial activity were all implicated in the development of these effects. Keywords: anxiety, cognitive impairment, depression, diabetes, minocycline