Department of Regulatory Toxicology, National Institute of Pharmaceutical Education and Research-Raebareli (NIPER-R), Transit Campus, Bijnor-Sisendi Road, Sarojini Nagar, Near CRPF Base Camp, Lucknow, UP 226002, India.
Department of Psychiatry, Center for Molecular Biology and Genetics of Neurodegeneration, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States of America.
Sci Total Environ. 2024 Dec 10;955:176941. doi: 10.1016/j.scitotenv.2024.176941. Epub 2024 Oct 23.
Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals widely used in various products, including food packaging, textiles, and firefighting foam, owing to their unique properties such as amphiphilicity and strong CF bonds. Despite their widespread use, concerns have arisen due to their resistance to degradation and propensity for bioaccumulation in both environmental and human systems. Emerging evidence suggests a potential link between PFAS exposure and neurotoxic effects, spanning cognitive deficits, neurodevelopmental disorders, and neurodegenerative diseases. This review comprehensively synthesizes current knowledge on PFAS neurotoxicity, drawing insights from epidemiological studies, animal experiments, and mechanistic investigations. PFAS, known for their lipophilic nature, tend to accumulate in lipid-rich tissues, including the brain, breaching biological barriers such as the blood-brain barrier (BBB). The accumulation of PFAS within the central nervous system (CNS) has been implicated in a spectrum of neurological maladies. Neurotoxicity induced by PFAS manifests through a multitude of direct and indirect mechanisms. A growing body of research associated PFAS exposure with BBB disruption, calcium dysregulation, neurotransmitter alterations, neuroinflammation, oxidative stress, and mitochondrial dysfunction, all contributing to neuronal impairment. Despite notable strides in research, significant lacunae persist, necessitating further exploration to elucidate the full spectrum of PFAS-mediated neurotoxicity. Prospective research endeavors should prioritize developing biomarkers, delineating sensitive exposure windows, and exploring mitigation strategies aimed at safeguarding neurological integrity within populations vulnerable to PFAS exposure.
全氟和多氟烷基物质（PFAS）是一种广泛应用于各种产品的合成化学品，包括食品包装、纺织品和消防泡沫，这要归功于它们独特的性质，如两亲性和强 CF 键。尽管它们被广泛使用，但由于其抗降解性和在环境和人体系统中生物累积的倾向，人们对它们产生了担忧。新出现的证据表明，PFAS 暴露与神经毒性效应之间存在潜在联系，包括认知缺陷、神经发育障碍和神经退行性疾病。这篇综述全面综合了目前关于 PFAS 神经毒性的知识，从流行病学研究、动物实验和机制研究中汲取了见解。由于其亲脂性，PFAS 往往会在富含脂质的组织中积累，包括大脑，突破血脑屏障（BBB）等生物屏障。PFAS 在中枢神经系统（CNS）内的积累与一系列神经疾病有关。PFAS 引起的神经毒性通过多种直接和间接机制表现出来。越来越多的研究将 PFAS 暴露与 BBB 破坏、钙失调、神经递质改变、神经炎症、氧化应激和线粒体功能障碍联系起来，所有这些都导致神经元损伤。尽管在研究方面取得了显著进展，但仍存在显著的空白，需要进一步探索，以阐明 PFAS 介导的神经毒性的全貌。前瞻性研究应优先开发生物标志物，划定敏感的暴露窗口，并探索旨在保护易受 PFAS 暴露影响的人群神经完整性的缓解策略。
