Neurotransmission Targets of Per- and Polyfluoroalkyl Substance Neurotoxicity: Mechanisms and Potential Implications for Adverse Neurological Outcomes.
Neurotransmission Targets of Per- and Polyfluoroalkyl Substance Neurotoxicity: Mechanisms and Potential Implications for Adverse Neurological Outcomes.
复制标题
DOI：
10.1021/acs.chemrestox.2c00072
复制
发表时间：
2022-08-15
影响因子：
4.1
通讯作者：
Cannon, Jason R.
中科院分区：
文献类型：
--
作者：
Brown-Leung, Josephine M.;Cannon, Jason R.
全氟烷基和多氟烷基物质（PFAS）是一组持久性环境污染物，普遍存在于环境中，几乎存在于包括人类在内的所有生物体中。PFAS通过血脑屏障并在脑中积聚。因此，PFAS可能具有神经毒性风险。测量人类、北极熊和大鼠大脑中PFAS水平的研究表明，大脑的某些区域积累了大量的PFAS。此外，在人类中，有证据表明PFAS暴露与儿童的注意力缺陷/多动障碍（ADHD）以及老年人群中帕金森病和阿尔茨海默病的死亡原因增加有关。鉴于与神经系统疾病可能存在联系，有必要对神经毒性作用的可能机制进行批判性分析，以推进该领域的发展。本文对神经毒性的潜在机制原因进行了综述，包括（1）神经递质水平的变化，（2）突触钙稳态功能障碍，（3）突触和神经元蛋白表达和功能的改变。我们发现越来越多的证据表明，PFAS暴露通过破坏神经传递，特别是多巴胺和谷氨酸系统，导致神经毒性，这与年龄相关的精神疾病和神经退行性疾病有关。评估研究表明，在PFAS暴露后，海马中的谷氨酸水平和下丘脑中的儿茶酚胺水平高度再现性地增加，而全脑中的多巴胺水平降低。在与人类中观察到的PFAS相关神经功能障碍相关的其他区域中，相对于黑质纹状体系统（纹状体和腹侧中脑）的评估，文献中存在显著差距。总之，有证据表明PFAS可能具有神经毒性，并与慢性和年龄相关的精神疾病和神经退行性疾病有关。因此，未来的机制研究必须评估PFAS和PFAS混合物对神经传递机制和相应的功能效应的影响。
Per- and polyfluoroalkyl substances (PFAS) are a group of persistent environmental pollutants that are ubiquitously found in the environment and virtually in all living organisms, including humans. PFAS cross the blood–brain barrier and accumulate in the brain. Thus, PFAS are a likely risk for neurotoxicity. Studies that measured PFAS levels in the brains of humans, polar bears, and rats have demonstrated that some areas of the brain accumulate greater amounts of PFAS. Moreover, in humans, there is evidence that PFAS exposure is associated with attention-deficit/hyperactivity disorder (ADHD) in children and an increased cause of death from Parkinson’s disease and Alzheimer’s disease in elderly populations. Given possible links to neurological disease, critical analyses of possible mechanisms of neurotoxic action are necessary to advance the field. This paper critically reviews studies that investigated potential mechanistic causes for neurotoxicity including (1) a change in neurotransmitter levels, (2) dysfunction of synaptic calcium homeostasis, and (3) alteration of synaptic and neuronal protein expression and function. We found growing evidence that PFAS exposure causes neurotoxicity through the disruption of neurotransmission, particularly the dopamine and glutamate systems, which are implicated in age-related psychiatric illnesses and neurodegenerative diseases. Evaluated research has shown there are highly reproduced increased glutamate levels in the hippocampus and catecholamine levels in the hypothalamus and decreased dopamine in the whole brain after PFAS exposure. There are significant gaps in the literature relative to the assessment of the nigrostriatal system (striatum and ventral midbrain) among other regions associated with PFAS-associated neurologic dysfunction observed in humans. In conclusion, evidence suggests that PFAS may be neurotoxic and associated with chronic and age-related psychiatric illnesses and neurodegenerative diseases. Thus, it is imperative that future mechanistic studies assess the impact of PFAS and PFAS mixtures on the mechanism of neurotransmission and the consequential functional effects.
登录
查看更多内容
影响因子：
2.9
作者：
Foguth, R. M.;Hoskins, T. D.;Cannon, J. R.
通讯作者：
Cannon, J. R.
影响因子：
11.4
作者：
Gronnestad, Randi;Vazquez, Berta Perez;Krokje, Ase
通讯作者：
Krokje, Ase
影响因子：
3.8
作者：
Berntsen, Hanne Friis;Bjorklund, Cesilie Granum;Ropstad, Erik
通讯作者：
Ropstad, Erik
影响因子：
6
作者：
Cope HA;Blake BE;Love C;McCord J;Elmore SA;Harvey JB;Chappell VA;Fenton SE
通讯作者：
Fenton SE
影响因子：
3.8
作者：
Gronnestad, Randi;Johanson, Silje Modahl;Arukwe, Augustine
通讯作者：
Arukwe, Augustine