2. Academic Validation
  3. Anti-depressive-like behaviors of APN KO mice involve Trkb/BDNF signaling related neuroinflammatory changes

Anti-depressive-like behaviors of APN KO mice involve Trkb/BDNF signaling related neuroinflammatory changes

  • Mol Psychiatry. 2022 Feb;27(2):1047-1058. doi: 10.1038/s41380-021-01327-3.
Weifen Li 1,  Tahir Ali 1,  Chengyou Zheng 1,  Kaiwu He 1,  Zizhen Liu 1,  Fawad Ali Shah 1 2,  Ningning Li 3 4,  Zhi-Jian Yu 5,  Shupeng Li 6 7 8
Affiliations

Affiliations

  • 1 State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
  • 2 Riphah Institute of Pharmaceutical Sciences Riphah International University Islamabad, Islamabad, Pakistan.
  • 3 Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.
  • 4 Tomas Lindahl Nobel Laureate Laboratory, Precision Medicine Research Centre, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, 518107, China.
  • 5 Department of Infectious Diseases and Shenzhen key laboratory for endogenous infections, the 6th Affiliated Hospital of Shenzhen University Health Science Center. No 89, Taoyuan Road, Nanshan District, Shenzhen, 518052, China. yuzhijiansmu@163.com.
  • 6 State Key Laboratory of Chemical Oncogenomics, School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China. lisp@pku.edu.cn.
  • 7 Campbell Research Institute, Centre for Addiction and Mental Health, Toronto, ON, Canada. lisp@pku.edu.cn.
  • 8 Department of Psychiatry, University of Toronto, Toronto, ON, Canada. lisp@pku.edu.cn.
PMID: 34642455 DOI: 10.1038/s41380-021-01327-3
Abstract

Major depression disorder is a severe mental illness often linked with metabolic disorders. Adiponectin is an adipocyte-secreted circulatory hormone with antidiabetic and glucose/lipid modulation capacities. Studies have demonstrated the pathophysiological roles of Adiponectin involved in various neurological disorders, including depression. However, the underlying mechanisms are poorly understood. Here we showed that Adiponectin deprivation enhanced antidepressive-like behaviors in the LPS-induced model of depression. APN KO mice displayed increased cytokines (both pro and anti-inflammatory), accompanied by an impaired expression of Adiponectin receptors (mRNA/protein level) and decreasing IBA-1 level in the cortex and primary microglia of LPS treated APN KO mice. Further, LPS-treatment significantly reduced p-NFκB expression in the microglia of APN KO mice. However, the Bay11-7082 treatment recovered p-NFκB expression in the cortex of APN KO mice in the presence of LPS. Interestingly, the antidepressant potentials of APN KO mice were abolished by TrkB Antagonist K252a, IKK Inhibitor Bay11-7082, and AdipoRon suggesting crosstalk between TrkB/BDNF signaling and NFκB in depression. Furthermore, the effects of Bay11-7082 were abolished by a TrkB/BDNF activator (7,8-DHF), indicating a critical role of TrkB/BDNF signaling. Taken together, these findings showed that dysregulated neuroinflammatory status and BDNF signaling might underlie the antidepressive-like behaviors of APN KO mice. NFκB elicited BDNF changes may be accountable for the pathogenesis of LPS induced depression, where APN might present an alternative therapeutic target for depressive disorders.

Figures
Products