Mitochondrial and inflammatory dysfunctions underlie perfluorooctane sulfonic acid (PFOS)-induced neurotoxicity in adult zebrafish

IF 8 1区环境科学与生态学 Q1 ENVIRONMENTAL SCIENCES

Science of the Total Environment Pub Date : 2025-06-25 DOI:10.1016/j.scitotenv.2025.179972

Gabriel Teixeira de Macedo , Mariana Torri Claro , Sabrina Antunes Ferreira , Julia Sepel Loreto , Babajide Oluwaseun Ajayi , Alessandro de Souza Prestes , Isaac Adegboyega Adedara , Talise Ellwanger Müller , Matheus Mülling dos Santos , Nilda de Vargas Barbosa

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Abstract

Perfluorooctane sulfonic acid (PFOS) is a persistent environmental contaminant widely detected in aquatic ecosystems and associated with neurotoxicity. However, the mechanisms underlying its neurological effects remain unclear. This study investigated acute and chronic neurotoxic effects of PFOS in adult zebrafish (Danio rerio), focusing on behavioral alterations, mitochondrial dysfunction, neuroinflammation, and histological abnormalities in different brain regions. Adult zebrafish were exposed to PFOS at 0.1, 1, and 10 μM for 30 min (acute) and 14 days (chronic). Behavioral assays evaluated exploration, social preference, and aggression. High-resolution respirometry assessed brain mitochondrial functionality, while gene expression and histological analyses examined markers of neuroinflammation, neural plasticity, and cell death after chronic exposure. Acute exposure showed no significant behavioral changes but trends of reduced exploration and aggression. Chronic exposure at 10 μM significantly reduced aggression. Mitochondrial respirometry revealed contrasting effects between acute and chronic exposures: acute PFOS resulted in increased oxidative phosphorylation capacity and bioenergetic efficiency, while chronic exposure impaired oxidative phosphorylation, bioenergetic efficiency, and electron transport chain activity. Gene expression supported dysregulation in mitochondrial dynamics, with mffa and mfn1a downregulated. Additionally, inflammation-related genes (il6, il10) and apoptosis/neural activation-related genes (casp3a, cyc1, fosaa, egr1) were altered. Histopathological evaluation showed neuronal vacuolation, architectural disorganization, cell damage, and increased inflammation in telencephalon, optic tectum, and cerebellum reinforcing neurotoxicity. Our findings indicate mitochondrial dysfunction and inflammatory dysregulation are key events underlying PFOS-induced neurotoxicity in adult zebrafish. Given the environmental persistence and bioaccumulative nature of PFOS, further research is needed to assess long-term neurotoxic risks and develop mitigation strategies.

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线粒体和炎症功能障碍是全氟辛烷磺酸（PFOS）诱导成年斑马鱼神经毒性的基础

全氟辛烷磺酸（PFOS）是一种广泛存在于水生生态系统中的持久性环境污染物，具有神经毒性。然而，其神经效应的机制尚不清楚。本研究研究了全氟辛烷磺酸对成年斑马鱼（Danio rerio）的急性和慢性神经毒性作用，重点研究了不同大脑区域的行为改变、线粒体功能障碍、神经炎症和组织学异常。成年斑马鱼分别暴露于0.1、1和10 μM的全氟辛烷磺酸环境30分钟（急性）和14天（慢性）。行为分析评估探索、社会偏好和攻击性。高分辨率呼吸测量法评估了脑线粒体功能，而基因表达和组织学分析检查了慢性暴露后神经炎症、神经可塑性和细胞死亡的标志物。急性暴露没有显著的行为改变，但有探索和攻击减少的趋势。长期暴露在10 μM下可显著降低攻击行为。线粒体呼吸测量显示急性和慢性暴露对PFOS的不同影响：急性PFOS导致氧化磷酸化能力和生物能量效率增加，而慢性暴露会损害氧化磷酸化、生物能量效率和电子传递链活性。基因表达支持线粒体动力学失调，mffa和mfn1a下调。此外，炎症相关基因（il6、il10）和凋亡/神经激活相关基因（casp3a、cyc1、fosaa、egr1）也发生了改变。组织病理学检查显示神经元空泡化、结构紊乱、细胞损伤以及端脑、视顶叶和小脑炎症增加，增强了神经毒性。我们的研究结果表明，线粒体功能障碍和炎症失调是成年斑马鱼全氟辛烷磺酸诱导的神经毒性的关键事件。鉴于全氟辛烷磺酸的环境持久性和生物蓄积性，需要进一步研究以评估长期神经毒性风险并制定缓解战略。

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来源期刊

Science of the Total Environment 环境科学-环境科学

CiteScore

17.60

自引率

10.20%

发文量

8726

审稿时长

2.4 months

期刊介绍： The Science of the Total Environment is an international journal dedicated to scientific research on the environment and its interaction with humanity. It covers a wide range of disciplines and seeks to publish innovative, hypothesis-driven, and impactful research that explores the entire environment, including the atmosphere, lithosphere, hydrosphere, biosphere, and anthroposphere. The journal's updated Aims & Scope emphasizes the importance of interdisciplinary environmental research with broad impact. Priority is given to studies that advance fundamental understanding and explore the interconnectedness of multiple environmental spheres. Field studies are preferred, while laboratory experiments must demonstrate significant methodological advancements or mechanistic insights with direct relevance to the environment.