Kumari Yatinesh, Choo Brandon Kar Meng, Shaikh Mohd Farooq, Othman Iekhsan
Neuropharmacology Research Laboratory, Jeffrey Cheah School of Medicine and Health Sciences, Monash University, Subang Jaya, Selangor 47500, Malaysia.
Exp Ther Med. 2019 Aug;18(2):1407-1416. doi: 10.3892/etm.2019.7685. Epub 2019 Jun 18.
Early life exposure to stress has been suggested to be a crucial factor for the development of the brain and its functions. It is well documented that childhood stress is a risk factor for sleep problems in adulthood. . leaf extract (PB) has been used in several traditional medicines to cure various ailments. Recently, PB has been proved to have antidepressant activity. The literature suggests that antidepressants affect the synthesis and release of melatonin through several mechanisms. Thus, this study investigated the potential role of PB for the treatment of sleep disruption after early life stress exposure. Firstly, dexamethasone (DEX) (2 and 20 mg/l for 24 h) was administered to zebrafish larvae on the 4th day post-fertilization (dpf) to induce early life stress. The effects of stress on behaviour during adulthood, melatonin level and stress-related gene expression () in the brain were then studied. Next, the possible role of PB (10 and 30 mg/Kg) was studied by measuring its effect on behaviour and by quantifying the expression levels of several melatonin-related () and stress-related () genes by qPCR. DEX-treated zebrafish exhibited anxious behaviour, along with a lower level of melatonin and a higher mRNA expression of . After treatment with PB, a similar effect on behaviour and gene expression levels as the melatonin treatment group (10 mg/kg; positive control) was seen in adult zebrafish. These molecular confirmations of the observed behavioural effects of the PB indicate a possible role in the treatment of early life stress-induced sleep disruption.
早年暴露于应激被认为是大脑发育及其功能形成的关键因素。有充分的文献记载,童年期应激是成年后睡眠问题的一个风险因素。……叶提取物(PB)已被用于多种传统药物中治疗各种疾病。最近,PB已被证明具有抗抑郁活性。文献表明,抗抑郁药通过多种机制影响褪黑素的合成和释放。因此,本研究调查了PB在治疗早年应激暴露后睡眠障碍方面的潜在作用。首先,在受精后第4天(dpf)给斑马鱼幼体施用24小时的地塞米松(DEX)(2和20mg/l)以诱导早年应激。然后研究应激对成年期行为、褪黑素水平以及大脑中应激相关基因表达(……)的影响。接下来,通过测量PB(10和30mg/Kg)对行为的影响以及通过qPCR定量几种褪黑素相关(……)和应激相关(……)基因的表达水平,研究其可能的作用。DEX处理的斑马鱼表现出焦虑行为,同时褪黑素水平较低且……的mRNA表达较高。用PB处理后,成年斑马鱼在行为和基因表达水平上出现了与褪黑素治疗组(10mg/kg;阳性对照)类似的效果。这些对PB观察到的行为效应的分子证实表明其在治疗早年应激诱导的睡眠障碍中可能发挥作用。