Burke Richard D, Todd Spencer W, Lumsden Eric, Mullins Roger J, Mamczarz Jacek, Fawcett William P, Gullapalli Rao P, Randall William R, Pereira Edna F R, Albuquerque Edson X
Division of Translational Toxicology, Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, Maryland, USA.
Department of Diagnostic Radiology, University of Maryland School of Medicine, Baltimore, Maryland, USA.
J Neurochem. 2017 Aug;142 Suppl 2(Suppl 2):162-177. doi: 10.1111/jnc.14077.
Organophosphorus (OP) insecticides are pest-control agents heavily used worldwide. Unfortunately, they are also well known for the toxic effects that they can trigger in humans. Clinical manifestations of an acute exposure of humans to OP insecticides include a well-defined cholinergic crisis that develops as a result of the irreversible inhibition of acetylcholinesterase (AChE), the enzyme that hydrolyzes the neurotransmitter acetylcholine (ACh). Prolonged exposures to levels of OP insecticides that are insufficient to trigger signs of acute intoxication, which are hereafter referred to as subacute exposures, have also been associated with neurological deficits. In particular, epidemiological studies have reported statistically significant correlations between prenatal subacute exposures to OP insecticides, including chlorpyrifos, and neurological deficits that range from cognitive impairments to tremors in childhood. The primary objectives of this article are: (i) to address the short- and long-term neurological issues that have been associated with acute and subacute exposures of humans to OP insecticides, especially early in life (ii) to discuss the translational relevance of animal models of developmental exposure to OP insecticides, and (iii) to review mechanisms that are likely to contribute to the developmental neurotoxicity of OP insecticides. Most of the discussion will be focused on chlorpyrifos, the top-selling OP insecticide in the United States and throughout the world. These points are critical for the identification and development of safe and effective interventions to counter and/or prevent the neurotoxic effects of these chemicals in the developing brain. This is an article for the special issue XVth International Symposium on Cholinergic Mechanisms.
有机磷（OP）杀虫剂是全球广泛使用的害虫防治剂。不幸的是，它们对人类可能产生的毒性作用也广为人知。人类急性接触OP杀虫剂的临床表现包括因乙酰胆碱酯酶（AChE）被不可逆抑制而引发的明确胆碱能危象，AChE是一种水解神经递质乙酰胆碱（ACh）的酶。长期接触不足以引发急性中毒症状的OP杀虫剂水平（以下简称亚急性接触）也与神经功能缺损有关。特别是，流行病学研究报告称，产前亚急性接触包括毒死蜱在内的OP杀虫剂与从认知障碍到儿童期震颤等一系列神经功能缺损之间存在统计学上的显著相关性。本文的主要目标是：（i）探讨与人类急性和亚急性接触OP杀虫剂相关的短期和长期神经问题，尤其是在生命早期；（ii）讨论发育性接触OP杀虫剂动物模型的转化相关性；（iii）综述可能导致OP杀虫剂发育性神经毒性的机制。大部分讨论将集中在毒死蜱上，它是美国乃至全球最畅销的OP杀虫剂。这些要点对于识别和开发安全有效的干预措施以对抗和/或预防这些化学物质对发育中大脑的神经毒性作用至关重要。这是一篇发表于第十五届国际胆碱能机制研讨会特刊的文章。
