Effect of aerobic exercise as a treatment on type 2 diabetes mellitus with depression-like behavior zebrafish

Background Depression is the most known complication of type 2 diabetes mellitus (T2DM). Aerobic exercise improves glycemic control in T2DM, although the underlying mechanisms of comorbid depression-like behaviors in T2DM have not yet been fully elucidated. Methods 120 zebrafish were randomly assigned to four groups: Control, T2DM, T2DM + metformin, and T2DM + aerobic exercise. Then, all animals except the control group were fed with high glucose fairy shrimp (~40 g/kg/day) and exposed reserpine (40 μg/ml for 20 min) for 10 days. Here, behavioral tests were used for model verification. Following the verification, all groups were treated as before. Additionally, the T2DM + metformin group received metformin (~10.6 mg/kg/day) at the same time, while the T2DM + aerobic exercise group received aerobic exercise 30 min/day. Finally, blood glucose and behavioral tests, as well as protein and molecular levels were determined at Day 11 and 12. Results Aerobic exercise alleviated depressive-like behavior and enhanced the levels of antidepressant biomarkers (NE, 5-HIAA) in zebrafish after 10 consecutive days of exercise. Additionally, 10 consecutive days of aerobic exercise decreased the levels of inflammatory biomarkers (IFN-γ, IL-1, IL-4) and depressive biomarkers (cortisol). Meanwhile, it also aided in the reduction of CD11b, IL-6, IL-6R, and caspase-3 expression to combat the neuroinflammation induced by T2DM, mediated the BDNF-TrkB pathway, and increased Bcl-2/Bax levels. Conclusion Given the remarkable similarity in neurochemistry between humans and zebrafish, this study supports the effectiveness of aerobic exercise as clinical guidance in preventing and treating T2DM complicated with depression.