Department of Biochemistry, North Eastern Hill University, Shillong, 793 022, Meghalaya, India.
Department of Biochemistry, North Eastern Hill University, Shillong, 793 022, Meghalaya, India.
Behav Brain Res. 2020 Sep 1;393:112780. doi: 10.1016/j.bbr.2020.112780. Epub 2020 Jun 21.
Anxiety and depression are among the major neuropsychiatric disorders worldwide, and yet the etiologies of these disorders remain unclear to date. Chronic unpredictable stress (CUS) procedure mimics several behavioral characteristics such as anxiety and depression in rodents. Using this animal model, we have attempted to understand the serotonergic system in the hippocampus and prefrontal cortex, while using the 5-HTR agonist and antagonist in evaluating 5-HT receptor neurotransmission. A decrease in serotonin (5-HT) level, tryptophan hydroxylase-2 activity and, 5-HTR receptor protein down-regulation in the CUS exposed group, explains the involvement of 5-HT and 5-HTR neurotransmission in the genesis of anxiety and depression. Besides, the oxidative stress - attenuated electrolyte imbalance via decrease ATPase pump activity, and compromised oxidative phosphorylation via decrease ETC-I activity are some of the underlying factors affecting neuronal cell survival and serotonergic neurotransmission. To complement our finding, altered behavioral performance scored in the open field test, elevated plus maze test, and the forced swim test, when exposed to CUS is indicative or consistent with anxiety, depression, emotional and locomotor status of the animals. Keeping these findings in mind, treatment with 5-HTR agonist (1-Methylpsilocin at 0.7 mg/kg), and 5-HTR antagonist (RS-102221 hydrochloride at 1 mg/kg) displayed varying results. One prominent finding was the anxiolytic ability of the 5-HTR agonist and the anti-depressive ability of the 5-HTR antagonist on the 7th-day treatment. Though the exact mechanism of action is not clear, their ability to equilibrate brain redox status, restoring Ca level via CaATPase pump activity, and sustaining the mitochondrial bioenergetics can all be accounted for facilitating neurogenesis and the serotonergic system.
焦虑症和抑郁症是全球范围内主要的神经精神疾病，而这些疾病的病因至今仍不清楚。慢性不可预测应激（CUS）程序模拟了啮齿动物的焦虑和抑郁等几种行为特征。使用这种动物模型，我们试图了解海马体和前额叶皮层中的 5-羟色胺能系统，同时使用 5-HT 激动剂和拮抗剂来评估 5-HT 受体神经传递。CUS 暴露组中 5-羟色胺（5-HT）水平、色氨酸羟化酶-2 活性和 5-HT 受体蛋白下调，解释了 5-HT 和 5-HT 受体神经传递在焦虑和抑郁发生中的作用。此外，氧化应激通过降低 ATP 酶泵活性减弱电解质失衡，并通过降低 ETC-I 活性破坏氧化磷酸化，是影响神经元细胞存活和 5-羟色胺能神经传递的一些潜在因素。为了补充我们的发现，在暴露于 CUS 时，旷场试验、高架十字迷宫试验和强迫游泳试验中改变的行为表现评分表明动物的焦虑、抑郁、情绪和运动状态发生了变化。考虑到这些发现，5-HT 激动剂（1-甲基色胺在 0.7mg/kg）和 5-HT 拮抗剂（RS-102221 盐酸盐在 1mg/kg）的治疗显示出不同的结果。一个突出的发现是 5-HT 激动剂的抗焦虑作用和 5-HT 拮抗剂的抗抑郁作用在第 7 天治疗时。虽然确切的作用机制尚不清楚，但它们平衡大脑氧化还原状态、通过 CaATP 酶泵活性恢复 Ca 水平以及维持线粒体生物能的能力都可以解释促进神经发生和 5-羟色胺能系统。
