Ketamine Alleviates Postoperative Depression-Like Symptoms in Susceptible Mice: The Role of BDNF-TrkB Signaling

Shan Li; Xiaoxiao Luo; Dongyu Hua; Yue Wang; Gaofeng Zhan; Niannian Huang; Riyue Jiang; Ling Yang; Bin Zhu; Xianglin Yuan; Ailin Luo; Chun Yang

doi:10.3389/fphar.2019.01702

Ketamine Alleviates Postoperative Depression-Like Symptoms in Susceptible Mice: The Role of BDNF-TrkB Signaling

Front Pharmacol. 2020 Feb 6:10:1702. doi: 10.3389/fphar.2019.01702. eCollection 2019.

Authors

Shan Li¹, Xiaoxiao Luo¹, Dongyu Hua¹, Yue Wang¹, Gaofeng Zhan¹, Niannian Huang¹, Riyue Jiang², Ling Yang², Bin Zhu², Xianglin Yuan³, Ailin Luo¹, Chun Yang⁴

Affiliations

¹ Department of Anesthesiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
² Department of Internal Medicine, The Third Affiliated Hospital of Soochow University, Changzhou, China.
³ Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Abstract

Patients are more likely to suffer from central nervous system (CNS) complications after anesthesia and surgery. However, postoperative depression (POD) has not yet received sufficient attentions, and its pathogenesis and therapeutic strategies remain poorly understood. We here aimed to investigate whether brain derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) signaling plays an important role in POD. BDNF-TrkB signaling was altered in brain and peripheral tissues, including medial prefrontal cortex (mPFC), hippocampus, liver, and muscle, among control, POD susceptible, and resilient groups. Additionally, we demonstrated that 7,8-dihydroxyflavone (7,8-DHF), a TrkB agonist, could exert its pharmacologic property to alleviate POD-like symptoms. More importantly, ketamine, a non-competitive N-methyl-D-aspartic acid (NMDA) receptor antagonist, also has significant antidepressant effects in POD model, associating with the improving effects on levels of BDNF-TrkB signaling in brain and peripheral tissues. Interestingly, the beneficial effects of ketamine on POD-like symptoms are fully attenuated by a TrkB antagonist. These findings suggest that abnormal expressions of BDNF-TrkB signaling in brain and peripheral tissues are implicated in the pathogenesis of POD, and that therapeutic agents targeting BDNF-TrkB, particularly ketamine, could favor the beneficial effects for POD.

Keywords: BDNF-TrkB signaling; elderly; ketamine; postoperative depression; sex difference.