Depression is one of the most common mental illnesses. However, the pathogenesis and underlying neurobiology of depression remain poorly understood and not all depressed patients respond to current available treatments. Our recent studies have identified a role for leptin a hormone secreted from adipose tissue, in emotional processes and demonstrated that leptin has the potential as a novel antidepressant. The goal of this project is to elucidate the neural mechanisms underlying the antidepressant-like effects of leptin. First, we plan to investigate the potential role of leptin in hippocampal neurogenesis. Second, the importance of leptin action on the hippocampus in emotional behaviors will be addressed using both pharmacological and genetic approaches. Third, we will investigate the functional interaction between leptin and the serotonergic system. Our main hypothesis is that leptin's antidepressant-like activity is mediated by specific brain circuits and neurotransmitters. These studies will contribute to mechanistic understanding of the role of leptin in depression and provide insights into novel therapeutic approaches for the treatment of depressive disorders.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH076929-04
Application #
7749538
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Winsky, Lois M
Project Start
2007-01-25
Project End
2011-12-31
Budget Start
2010-01-01
Budget End
2010-12-31
Support Year
4
Fiscal Year
2010
Total Cost
$310,250
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Pharmacology
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Guo, M; Li, C; Lei, Y et al. (2017) Role of the adipose PPAR?-adiponectin axis in susceptibility to stress and depression/anxiety-related behaviors. Mol Psychiatry 22:1056-1068
Zhang, D; Wang, X; Wang, B et al. (2017) Adiponectin regulates contextual fear extinction and intrinsic excitability of dentate gyrus granule neurons through AdipoR2 receptors. Mol Psychiatry 22:1044-1055
Zhang, Di; Wang, Xuezhen; Lu, Xin-Yun (2016) Adiponectin Exerts Neurotrophic Effects on Dendritic Arborization, Spinogenesis, and Neurogenesis of the Dentate Gyrus of Male Mice. Endocrinology 157:2853-69
Liu, Jing; Guo, Ming; Lu, Xin-Yun (2015) Leptin/LepRb in the Ventral Tegmental Area Mediates Anxiety-Related Behaviors. Int J Neuropsychopharmacol 19:
Carrier, Nicole; Wang, Xuezhen; Sun, Linshan et al. (2015) Sex-Specific and Estrous Cycle-Dependent Antidepressant-Like Effects and Hippocampal Akt Signaling of Leptin. Endocrinology 156:3695-705
Wang, X; Zhang, D; Lu, X-Y (2015) Dentate gyrus-CA3 glutamate release/NMDA transmission mediates behavioral despair and antidepressant-like responses to leptin. Mol Psychiatry 20:509-19
Liu, Jing; Garza, Jacob C; Li, Wei et al. (2013) Melanocortin-4 receptor in the medial amygdala regulates emotional stress-induced anxiety-like behaviour, anorexia and corticosterone secretion. Int J Neuropsychopharmacol 16:105-20
Guo, Ming; Huang, Tung-Yi; Garza, Jacob C et al. (2013) Selective deletion of leptin receptors in adult hippocampus induces depression-related behaviours. Int J Neuropsychopharmacol 16:857-67
Guo, Ming; Lu, Yuan; Garza, Jacob C et al. (2012) Forebrain glutamatergic neurons mediate leptin action on depression-like behaviors and synaptic depression. Transl Psychiatry 2:e83
Garza, J C; Guo, M; Zhang, W et al. (2012) Leptin restores adult hippocampal neurogenesis in a chronic unpredictable stress model of depression and reverses glucocorticoid-induced inhibition of GSK-3ýý/ýý-catenin signaling. Mol Psychiatry 17:790-808

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