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.
Highlights
Everyone will encounter a condition which needs effective treatment involving in surgery and anesthesia
We found TST immobility time was significantly increased on day 1, 15, and 22, but not on day 8, after anesthesia and surgery (Figure 1C), while Forced swimming test (FST) immobility time was significantly increased on day 2, 9, 16, and 23 postoperatively (Figure 1D)
Levels of brain derived neurotrophic factor (BDNF)-tropomyosin-related kinase B (TrkB) signaling were significantly lower in brain and peripheral tissues in postoperative depression (POD) susceptible mice than those in control or resilient group
Summary
Everyone will encounter a condition which needs effective treatment involving in surgery and anesthesia. Approximately 15 % of patients undergoing various surgeries are at higher risk of central nervous system (CNS) complications, leading to 80 % of all deaths during perioperative period (Ghoneim and O'Hara, 2016). Meta-analysis of randomized controlled trials provide a strong evidence that perioperative depression was significantly correlated with the early and later morality in patients undergoing cardiac surgery (Jiang et al, 2016). It has been demonstrated that patients with postoperative depression (POD) are prone to suffer from increased incidences of infections, cognitive dysfunction, and mortality from cancer postoperatively (Ghoneim and O'Hara, 2016). Little academic attentions have been focused on POD, and more importantly, its pathogenesis and therapeutic mechanisms remain unknown
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