Wang Lei, Ma Jiahui, Wu Wei, Fang Yimeng, Liu Fan, Yang Qinsi, Hu Xiang, Gu Xuejiang, He Zhiying, Sun Da, Jin Libo, Zhang Xingxing
Institute of Life Sciences & Biomedical Collaborative Innovation Center of Zhejiang Province, Wenzhou University, Wenzhou 325035, China.
Key Laboratory for Biorheological Science and Technology of Ministry of Education, State and Local Joint Engineering Laboratory for Vascular Implants, Bioengineering College of Chongqing University, Chongqing 400044, China.
Life Sci. 2022 Jul 1;300:120578. doi: 10.1016/j.lfs.2022.120578. Epub 2022 Apr 27.
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.
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.
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.
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.
抑郁症是2型糖尿病（T2DM）最常见的并发症。有氧运动可改善T2DM患者的血糖控制，尽管T2DM合并抑郁样行为的潜在机制尚未完全阐明。
120条斑马鱼随机分为四组：对照组、T2DM组、T2DM + 二甲双胍组和T2DM + 有氧运动组。然后，除对照组外，所有动物均喂食高糖丰年虾（约40 g/kg/天），并暴露于利血平（40 μg/ml，持续20分钟）10天。在此，通过行为测试进行模型验证。验证后，所有组继续按之前的方式处理。此外，T2DM + 二甲双胍组同时给予二甲双胍（约10.6 mg/kg/天），而T2DM + 有氧运动组每天进行30分钟的有氧运动。最后，在第11天和第12天测定血糖、行为测试以及蛋白质和分子水平。
连续10天运动后，有氧运动减轻了斑马鱼的抑郁样行为，并提高了抗抑郁生物标志物（去甲肾上腺素、5-羟吲哚乙酸）的水平。此外，连续10天有氧运动降低了炎症生物标志物（干扰素-γ、白细胞介素-1、白细胞介素-4）和抑郁生物标志物（皮质醇）的水平。同时，它还有助于降低CD11b、白细胞介素-6、白细胞介素-6受体和半胱天冬酶-3的表达，以对抗T2DM诱导的神经炎症，介导脑源性神经营养因子-酪氨酸激酶B通路，并提高Bcl-2/Bax水平。
鉴于人类和斑马鱼在神经化学方面具有显著相似性，本研究支持有氧运动作为预防和治疗T2DM合并抑郁症的临床指导的有效性。
