title: Leptin receptor knockout-induced depression-like behaviors and attenuated antidepressant effects of exercise are associated with STAT3/SOCS3 signaling.
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.
authors.affiliation: 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.
authors.forename: Weina
authors.initials: W
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Jiatong
authors.initials: J
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Jie
authors.initials: J
authors.lastname: Xia
authors.affiliation: 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.
authors.forename: Xiangli
authors.initials: X
authors.lastname: Xue
authors.affiliation: 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.
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Zhengtang
authors.initials: Z
authors.lastname: Qi
authors.affiliation: 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.
authors.forename: Liu
authors.initials: L
authors.lastname: Ji
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D003863:Depression / Q000235:genetics* / Q000378:metabolism; D004195:Disease Models, Animal; D051379:Mice; D018345:Mice, Knockout; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*; D054411:Receptors, Leptin / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000378:metabolism*
chemical_list: D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; D000071223:Suppressor of Cytokine Signaling 3 Protein
keywords: Depression; Exercise; IKKβ/NFκB signaling; Leptin receptor; STAT3/SOCS3 signaling