Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China; School of Physical Education & Health Care, East China Normal University, Shanghai 200241, China.
Key Laboratory of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, East China Normal University, Shanghai 200241, China; School of Physical Education & Health Care, East China Normal University, Shanghai 200241, China.
Brain Behav Immun. 2017 Mar;61:297-305. doi: 10.1016/j.bbi.2017.01.001. Epub 2017 Jan 7.
Relatively little has been known about pathophysiological mechanisms contributing to the development of neuropsychiatric symptoms in the context of metabolic syndrome. Impaired leptin signaling activation in db/db mice has been proposed as a potential link between behavioral and metabolic disorders. Our previous studies have shown that exercise has the beneficial effects on a depression-like and insulin-resistant state in mice. The present study aimed to determine whether and how leptin receptor knockout (db/db) induces depression-like behaviors, and to identify the antidepressant effects of swimming exercise in db/db mice. Our results support the validity of db/db mice as an animal model to study depression with metabolic abnormalities, but fail to confirm the improvement of exercise on depression. LepRb knockout-induced depression-like behaviors are associated with STAT3/SOCS3 signaling but independent of IKKβ/NFκB signaling. Our findings suggest the potential importance of LepRb as an exercise-regulated target for depression, also representing a new target underlying treatment-resistant depression.
关于代谢综合征背景下导致神经精神症状发生的病理生理机制，人们知之甚少。在 db/db 小鼠中，瘦素信号激活受损被认为是行为和代谢紊乱之间的潜在联系。我们之前的研究表明，运动对小鼠的抑郁样和胰岛素抵抗状态有有益的影响。本研究旨在确定瘦素受体敲除（db/db）是否以及如何引起抑郁样行为，并确定游泳运动对 db/db 小鼠的抗抑郁作用。我们的结果支持 db/db 小鼠作为研究具有代谢异常的抑郁症的动物模型的有效性，但未能证实运动对抑郁症的改善作用。LepRb 敲除诱导的抑郁样行为与 STAT3/SOCS3 信号有关，但与 IKKβ/NFκB 信号无关。我们的研究结果表明，LepRb 作为一种运动调节靶点在抑郁症中的潜在重要性，也代表了治疗抵抗性抑郁症的一个新靶点。
