Pharmacology and Drug Abuse Group, Convergence Toxicology Research Division, Korea Institute of Toxicology, KRICT, Daejeon 34114, Korea.
Department of Biomaterials Science, College of Natural Resources and Life Science/Life and Industry Convergence Research Institute, Pusan National University, Miryang 50463, Korea.
Int J Mol Sci. 2020 Nov 30;21(23):9103. doi: 10.3390/ijms21239103.
Depression is a serious medical illness that is one of the most prevalent psychiatric disorders. Corticosterone (CORT) increases depression-like behavior, with some effects on anxiety-like behavior. 2-Phenethylamine (PEA) is a monoamine alkaloid that acts as a central nervous system stimulant in humans. Here, we show that PEA exerts antidepressant effects by modulating the Brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB)/cAMP response element binding protein (CREB) signaling pathway in CORT-induced depression. To investigate the potential effects of PEA on CORT-induced depression, we first treated CORT (50 μM)-induced hippocampal neurons with 100 μM PEA for 24 h. We found that treatment with CORT altered dendritic spine architecture; however, treatment with PEA rescued dendritic spine formation via regulation of BDNF/TrkB/CREB signaling. Next, we used a mouse model of CORT-induced depression. Mice were treated with CORT (20 mg/kg) for 21 days, followed by assessments of a battery of depression-like behaviors. During the final four days of CORT exposure, the mice were treated with PEA (50 mg/kg). We found that CORT injection promoted depression-like behavior and significantly decreased BDNF and TrkB expression in the hippocampus. However, treatment with PEA significantly ameliorated the behavioral and biochemical changes induced by CORT. Our findings reveal that PEA exerts antidepressant effects by modulating the BDNF/TrkB/CREB signaling pathway in a mouse model of CORT-induced depression.
抑郁症是一种严重的医学疾病，也是最常见的精神障碍之一。皮质酮（CORT）增加了类似抑郁的行为，同时也对类似焦虑的行为产生了一些影响。2-苯乙胺（PEA）是一种单胺生物碱，在人类中作为中枢神经系统兴奋剂。在这里，我们表明 PEA 通过调节脑源性神经营养因子（BDNF）/原肌球蛋白受体激酶 B（TrkB）/环磷酸腺苷反应元件结合蛋白（CREB）信号通路在 CORT 诱导的抑郁中发挥抗抑郁作用。为了研究 PEA 对 CORT 诱导的抑郁的潜在影响，我们首先用 100μM 的 PEA 处理 CORT（50μM）诱导的海马神经元 24 小时。我们发现 CORT 处理改变了树突棘结构；然而，PEA 通过调节 BDNF/TrkB/CREB 信号来挽救树突棘形成。接下来，我们使用了 CORT 诱导的抑郁小鼠模型。小鼠用 CORT（20mg/kg）处理 21 天，然后进行一系列类似抑郁行为的评估。在 CORT 暴露的最后四天，用 PEA（50mg/kg）处理小鼠。我们发现 CORT 注射促进了类似抑郁的行为，并显著降低了海马体中的 BDNF 和 TrkB 表达。然而，PEA 处理显著改善了 CORT 引起的行为和生化变化。我们的研究结果表明，PEA 通过调节 BDNF/TrkB/CREB 信号通路在 CORT 诱导的抑郁小鼠模型中发挥抗抑郁作用。
