Microplastics Accumulation Induces Kynurenine-Derived Neurotoxicity in Cerebral Organoids and Mouse Brain.

IF 3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Sung Bum Park, Jeong Hyeon Jo, Seong Soon Kim, Won Hoon Jung, Myung Ae Bae, Byumseok Koh, Ki Young Kim
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引用次数: 0

Abstract

Microplastics are pervasive environmental pollutants with potential adverse effects on human health, particularly concerning neurotoxicity. This study investigates the accumulation and neurotoxic effects of MP in cerebral organoids and mouse brains. Utilizing in vitro cerebral organoids and in vivo mouse models, we examined the penetration of MP, revealing that smaller MP (50 nm) infiltrated deeper into the organoids compared to larger ones (100 nm). Exposure to 50 nm MP resulted in a significant reduction in organoid viability. Furthermore, total RNA sequencing indicated substantial alterations in neurotoxicity-related gene expression. In vivo, MP-treated mice exhibited notable DNA fragmentation in the hippocampus and cortex, alongside elevated levels of inflammatory markers and neurotoxic metabolites, such as kynurenine (KYN) and 3-hydroxykynurenine (3-HK). Our findings suggest that MP may promote neurotoxicity through the kynurenine pathway, leading to heightened levels of neurotoxic compounds like quinolinic acid. This research highlights the potential for MP to induce neuroinflammatory responses and disrupt normal brain function, underscoring the need for further investigation into the long-term effects of MP exposure on neurological health.

微塑料积累诱导犬尿氨酸来源的脑类器官和小鼠脑神经毒性。
微塑料是普遍存在的环境污染物,对人类健康具有潜在的不利影响,特别是在神经毒性方面。本研究探讨了MP在脑类器官和小鼠脑中的蓄积和神经毒性作用。利用体外脑类器官和体内小鼠模型,我们检测了MP的渗透,发现较小的MP (50 nm)比较大的MP (100 nm)渗透到类器官更深。暴露于50 nm的MP导致类器官活力显著降低。此外,总RNA测序显示神经毒性相关基因表达发生了实质性变化。在体内,mp处理的小鼠在海马和皮质中表现出明显的DNA断裂,同时炎症标志物和神经毒性代谢物水平升高,如犬尿氨酸(KYN)和3-羟基犬尿氨酸(3-HK)。我们的研究结果表明,MP可能通过犬尿氨酸途径促进神经毒性,导致喹啉酸等神经毒性化合物水平升高。这项研究强调了MP诱导神经炎症反应和破坏正常脑功能的潜力,强调了MP暴露对神经健康的长期影响的进一步研究的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
6.60
自引率
8.10%
发文量
72
审稿时长
6-12 weeks
期刊介绍: Biomolecules & Therapeutics (Biomolecules & Therapeutics) (Print ISSN 1976-9148, Online ISSN 2005-4483) is an international, peer-reviewed, open access journal that covers pharmacological and toxicological fields related to bioactive molecules and therapeutics. It was launched in 1993 as "The Journal of Applied Pharmacology (ISSN 1225-6110)", and renamed "Biomolecules & Therapeutics" (Biomol Ther: abbreviated form) in 2008 (Volume 16, No. 1). It is published bimonthly in January, March, May, July, September and November. All manuscripts should be creative, informative, and contribute to the development of new drugs. Articles in the following categories are published: review articles and research articles.
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