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Brain Behav Immun. 2017 Mar;61:297-305. doi: 10.1016/j.bbi.2017.01.001. Epub 2017 Jan 7.

Leptin receptor knockout-induced depression-like behaviors and attenuated antidepressant effects of exercise are associated with STAT3/SOCS3 signaling.

Author information

1
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.
2
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. Electronic address: qzht79@163.com.
3
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. Electronic address: lji@tyxx.ecnu.edu.cn.

Abstract

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.

KEYWORDS:

Depression; Exercise; IKKβ/NFκB signaling; Leptin receptor; STAT3/SOCS3 signaling

PMID:
28069387
DOI:
10.1016/j.bbi.2017.01.001
[Indexed for MEDLINE]

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