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汞暴露会损害儿茶酚胺能和胆碱能系统,导致黑腹果蝇的运动和非运动行为改变。

MeHg exposure impairs both the catecholaminergic and cholinergic systems resulting in motor and non-motor behavioral changes in Drosophila melanogaster.

机构信息

Universidade Federal do Pampa - Campus Uruguaiana, Programa de Pós-Graduação em Bioquímica (PPGBioq), Uruguaiana, RS, Brazil.

Laboratory of Molecular and Functional Neurobiology, Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, 05508-000, Brazil.

出版信息

Chem Biol Interact. 2022 Sep 25;365:110121. doi: 10.1016/j.cbi.2022.110121. Epub 2022 Aug 19.

Abstract

Human exposure to the natural environmental contaminant methylmercury (MeHg) has been associated to adverse health effects. Importantly, the mechanisms by which this organomercurial exerts its neurotoxicity have yet to be fully clarified. Therefore, the aim of this study was to evaluate whether exposure to MeHg alters dopamine (DA) and octopamine (OA) levels, acetylcholinesterase (AChE) activity and impacts both motor and non-motor behaviours. We studied the effect of MeHg by feeding 1-2 d old flies (male and females) with 25 and 50 μM MeHg for 4 d and determined effects on survival, motor and non-motor behaviours, oxidative stress, AChE and tyrosine hydroxylase (TH) activities, as well as DA and OA levels. We found that Drosophila melanogaster (D. melanogaster) exposed to MeHg showed a reduction in survival rate, associated with the inhibition of AChE and TH activities in head of flies and decreased DA and OA levels. These changes were accompanied by behavioural alterations, such as locomotor deficit and increased grooming behaviour, in addition to an increase in oxidative stress markers both in head and in body of flies, and an increase in glutathione-S-transferase (GST) activity in head of flies. Collectively, our data support the hypothesis that MeHg neurotoxicity is associated with altered OA and DA levels, AChE inhibition, which may serve, at least in part, as the underpinnings of both motor and non-motor behavioural changes.

摘要

人类暴露于自然环境污染物甲基汞(MeHg)与健康不良影响有关。重要的是,这种有机汞发挥其神经毒性的机制尚未完全阐明。因此,本研究旨在评估暴露于 MeHg 是否会改变多巴胺(DA)和章鱼胺(OA)水平、乙酰胆碱酯酶(AChE)活性,并影响运动和非运动行为。我们通过用 25 和 50 μM 的 MeHg 喂养 1-2 日龄的果蝇(雄性和雌性)4 天来研究 MeHg 的影响,并确定对存活率、运动和非运动行为、氧化应激、AChE 和酪氨酸羟化酶(TH)活性以及 DA 和 OA 水平的影响。我们发现,暴露于 MeHg 的黑腹果蝇(Drosophila melanogaster)表现出存活率降低,这与头部 AChE 和 TH 活性的抑制以及 DA 和 OA 水平的降低有关。这些变化伴随着行为改变,如运动缺陷和梳理行为增加,此外,头部和身体的氧化应激标志物增加,头部的谷胱甘肽-S-转移酶(GST)活性增加。总之,我们的数据支持了这样一种假设,即 MeHg 的神经毒性与 OA 和 DA 水平的改变、AChE 抑制有关,这至少部分是运动和非运动行为改变的基础。

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