Department of Anatomy, Faculty of Medicine, Universiti Kebangsaan Malaysia Medical Centre, Kuala Lumpur, Malaysia.
Department of Anatomy, Faculty of Medicine and Defence Health, National Defence University of Malaysia, Kuala Lumpur, Malaysia.
Int J Neurosci. 2023 Dec;133(8):822-833. doi: 10.1080/00207454.2021.1990916. Epub 2021 Oct 14.
Parkinson's disease (PD) is the second most common neurodegenerative disease caused by selective degeneration of dopaminergic neurons in the substantia nigra. Metallothionein has been shown to act as a neuroprotectant in various brain injury. Thus, this study aims to identify the effects of full-length human metallothionein 2 peptide (hMT2) in paraquat-induced brain injury in the zebrafish.
A total of 80 adult zebrafish were divided into 4 groups namely control, paraquat-treated, pre-hMT2-treated, and post-hMT2-treated groups. Fish were treated with paraquat intraperitoneally every 3 days for 15 days. hMT2 were injected intracranially on day 0 (pre-treated group) and day 16 (post-treated group). Fish were sacrificed on day 22 and the brains were collected for qPCR, ELISA and immunohistochemistry analysis.
qPCR analysis showed that paraquat treatment down-regulated the expression of genes related to dopamine activity and biosynthesis ( and ) and neuroprotective agent (). Paraquat treatment also up-regulated the expression of the , and proinflammatory genes (, , and ). hMT2 treatment was able to reverse the effects of paraquat. Lipid peroxidation decreased in the paraquat and pre-hMT2-treated groups. However, lipid peroxidation increased in the post-hMT2-treated group. Paraquat treatment also led to a reduction of dopaminergic neurons while their numbers showed an increase following hMT2 treatment.
Paraquat has been identified as one of the pesticides that can cause the death of dopaminergic neurons and affect dopamine biosynthesis. Treatment with exogenous hMT2 could reverse the effects of paraquat in the zebrafish brain.
帕金森病（PD）是由黑质中多巴胺能神经元选择性退化引起的第二大常见神经退行性疾病。金属硫蛋白已被证明在各种脑损伤中具有神经保护作用。因此，本研究旨在确定全长人金属硫蛋白 2 肽（hMT2）在百草枯诱导的斑马鱼脑损伤中的作用。
共 80 条成年斑马鱼分为 4 组，分别为对照组、百草枯处理组、hMT2 预处理组和 hMT2 后处理组。鱼用百草枯腹腔内注射，每 3 天 1 次，共 15 天。hMT2 于第 0 天（预处理组）和第 16 天（后处理组）脑内注射。第 22 天处死鱼，取脑进行 qPCR、ELISA 和免疫组织化学分析。
qPCR 分析显示，百草枯处理下调了与多巴胺活性和生物合成相关的基因（和）和神经保护剂（）的表达。百草枯处理还上调了、和促炎基因（、、和）的表达。hMT2 处理能够逆转百草枯的作用。百草枯和 hMT2 预处理组的脂质过氧化减少。然而，后处理组的脂质过氧化增加。百草枯处理还导致多巴胺能神经元减少，而 hMT2 处理后其数量增加。
百草枯已被确定为一种可导致多巴胺能神经元死亡并影响多巴胺生物合成的农药之一。外源性 hMT2 处理可逆转百草枯对斑马鱼大脑的影响。
