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暴露于邻苯二甲酸二(2-乙基己基)酯后协同的单胺氧化酶活性与斑马鱼大脑中的侵袭性行为反应和神经退行性变有关。

Concerted monoamine oxidase activity following exposure to di-2-ethylhexyl phthalate is associated with aggressive neurobehavioral response and neurodegeneration in zebrafish brain.

机构信息

Neurobiology Laboratory, Centre for Biotechnology, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar 751003, India.

Neurobiology Laboratory, Centre for Biotechnology, Siksha 'O' Anusandhan (Deemed to be University), Bhubaneswar 751003, India; Centre of Excellence, Natural Products and Therapeutics Laboratory, Department of Biotechnology and Bioinformatics, Sambalpur University, Odisha 768019, India.

出版信息

Comp Biochem Physiol C Toxicol Pharmacol. 2024 Sep;283:109970. doi: 10.1016/j.cbpc.2024.109970. Epub 2024 Jun 27.

Abstract

Di-2-ethylhexyl phthalate (DEHP) is the most commonly preferred synthetic organic chemical in plastics and its products for making them ductile, flexible and durable. As DEHP is not chemically bound to the macromolecular polymer of plastics, it can be easily leached out to accumulate in food and environment. Our recent report advocated that exposure to DEHP significantly transformed the innate bottom-dwelling and scototaxis behaviour of zebrafish. Our present study aimed to understand the possible role of DEHP exposure pertaining towards the development of aggressive behaviour and its association with amplified monoamine oxidase activity and neurodegeneration in the zebrafish brain. As heightened monoamine oxidase (MAO) is linked with genesis of aggressive behaviour, our observation also coincides with DEHP-persuaded aggressive neurobehavioral transformation in zebrafish. Our preliminary findings also showed that DEHP epitomized as a prime factor in transforming native explorative behaviour and genesis of aggressive behaviour through oxidative stress induction and changes in the neuromorphology in the periventricular grey zone (PGZ) of the zebrafish brain. With the finding demarcating towards heightened chromatin condensation in the PGZ of zebrafish brain, our further observation by immunohistochemistry showed a profound augmentation in apoptotic cell death marker cleaved caspase 3 (CC3) expression following exposure to DEHP. Our further observation by immunoblotting study also demarcated a temporal augmentation in CC3 and tyrosine hydroxylase expression in the zebrafish brain. Therefore, the gross findings of the present study delineate the idea that chronic exposure to DEHP is associated with MAO-instigated aggressive neurobehavioral transformation and neurodegeneration in the zebrafish brain.

摘要

邻苯二甲酸二(2-乙基己基)酯(DEHP)是塑料及其产品中最常用的合成有机化学品,用于使它们具有韧性、柔韧性和耐用性。由于 DEHP 与塑料的大分子聚合物没有化学键合,因此很容易浸出并积累在食物和环境中。我们最近的报告主张,接触 DEHP 会显著改变斑马鱼固有的底层和避光行为。我们目前的研究旨在了解 DEHP 暴露可能对攻击性行为的发展及其与斑马鱼大脑中单胺氧化酶活性增强和神经退行性变的关系。由于单胺氧化酶(MAO)升高与攻击性行为的发生有关,我们的观察结果也与 DEHP 诱导的斑马鱼攻击性神经行为转变一致。我们的初步研究结果还表明,DEHP 是通过诱导氧化应激和改变斑马鱼大脑室周灰质区(PGZ)的神经形态来转变固有探索行为和攻击性行为发生的主要因素。随着发现标志着斑马鱼大脑 PGZ 中染色质凝聚加剧,我们通过免疫组织化学进一步观察到,接触 DEHP 后,凋亡细胞死亡标志物 cleaved caspase 3(CC3)的表达明显增加。我们通过免疫印迹研究的进一步观察还表明,CC3 和酪氨酸羟化酶在斑马鱼大脑中的表达随时间增加。因此,本研究的总体结果表明,慢性接触 DEHP 与 MAO 引发的攻击性神经行为转变和斑马鱼大脑中的神经退行性变有关。

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