Wang Tianyuan, Weng Huandi, Zhou Hongji, Yang Zecheng, Tian Zhongyou, Xi Biao, Li Yalan
Department of Anesthesiology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, Guangdong, China.
Guangdong-Hongkong-Macau Institute of CNS Regeneration, Ministry of Education CNS Regeneration Collaborative Joint Laboratory, Jinan University, Guangzhou 510632, Guangdong, China.
J Affect Disord. 2022 Jun 15;307:97-107. doi: 10.1016/j.jad.2022.03.072. Epub 2022 Apr 1.
The rising incidence of postoperative depression (POD) in recent years has placed a heavy burden on patients' physical and mental health. At this point in time, however, POD pathogenesis remains poorly understood and novel therapeutic strategies are being sought. The present study aimed to clarify esketamine's protective effects and possible mechanisms of action in POD. To this avail, we used an animal model of postoperative depression to analyze behavioral, parameters, plus the inflammatory response in serum and in the medial prefrontal cortex (mPFC). Using immunofluorescence staining, we detected the number of microglia and parvalbumin (PV) in mPFC, and determined changes in neuronal dendritic spine density via Golgi staining. Expression of Iba1, PSD95 and NF-κB was examined by Western blot analysis. Our results show that esketamine can significantly improve depression-like symptoms caused by anesthesia and surgery. In addition, esketamine administration reversed the decrease in the density of PV neurons and restored synaptogenesis in mPFC which had been perturbed by inflammation. The evidence obtained suggests esketamine's anti-inflammatory effects may be mediated by the BDNF/TrkB signaling pathway and possibly by attenuation of the nuclear factor κB (NF-κB) pathway. These data warrant further investigations into the interplay of esketamine, and microglia in the modulation of POD symptomatology.
近年来，术后抑郁（POD）的发病率不断上升，给患者的身心健康带来了沉重负担。然而，目前对于POD的发病机制仍知之甚少，人们正在寻找新的治疗策略。本研究旨在阐明艾司氯胺酮在POD中的保护作用及其可能的作用机制。为此，我们使用术后抑郁动物模型分析行为参数以及血清和内侧前额叶皮质（mPFC）中的炎症反应。通过免疫荧光染色，我们检测了mPFC中小胶质细胞和小白蛋白（PV）的数量，并通过高尔基染色确定神经元树突棘密度的变化。通过蛋白质免疫印迹分析检测Iba1、PSD95和NF-κB的表达。我们的结果表明，艾司氯胺酮可以显著改善麻醉和手术引起的抑郁样症状。此外，给予艾司氯胺酮可逆转PV神经元密度的降低，并恢复mPFC中因炎症而受到干扰的突触形成。获得的证据表明，艾司氯胺酮的抗炎作用可能由BDNF/TrkB信号通路介导，也可能由核因子κB（NF-κB）通路的减弱介导。这些数据值得进一步研究艾司氯胺酮与小胶质细胞在调节POD症状方面的相互作用。
