Voorhees Jaymie R, Rohlman Diane S, Lein Pamela J, Pieper Andrew A
Department of Psychiatry, University of Iowa Carver College of MedicineIowa City, IA, USA; Interdisciplinary Graduate Program in Human Toxicology, University of Iowa Carver College of MedicineIowa City, IA, USA.
Interdisciplinary Graduate Program in Human Toxicology, University of Iowa Carver College of MedicineIowa City, IA, USA; Department of Occupational and Environmental Health, University of Iowa College of Public HealthIowa City, IA, USA.
Front Neurosci. 2017 Jan 18;10:590. doi: 10.3389/fnins.2016.00590. eCollection 2016.
Organophosphorus (OPs) compounds are widely used as insecticides, plasticizers, and fuel additives. These compounds potently inhibit acetylcholinesterase (AChE), the enzyme that inactivates acetylcholine at neuronal synapses, and acute exposure to high OP levels can cause cholinergic crisis in humans and animals. Evidence further suggests that repeated exposure to lower OP levels insufficient to cause cholinergic crisis, frequently encountered in the occupational setting, also pose serious risks to people. For example, multiple epidemiological studies have identified associations between occupational OP exposure and neurodegenerative disease, psychiatric illness, and sensorimotor deficits. Rigorous scientific investigation of the basic science mechanisms underlying these epidemiological findings requires valid preclinical models in which tightly-regulated exposure paradigms can be correlated with neurotoxicity. Here, we review the experimental models of occupational OP exposure currently used in the field. We found that animal studies simulating occupational OP exposures do indeed show evidence of neurotoxicity, and that utilization of these models is helping illuminate the mechanisms underlying OP-induced neurological sequelae. Still, further work is necessary to evaluate exposure levels, protection methods, and treatment strategies, which taken together could serve to modify guidelines for improving workplace conditions globally.
有机磷（OPs）化合物被广泛用作杀虫剂、增塑剂和燃料添加剂。这些化合物能有效抑制乙酰胆碱酯酶（AChE），该酶可使神经突触处的乙酰胆碱失活，急性接触高剂量的有机磷会导致人和动物出现胆碱能危象。有证据进一步表明，在职业环境中经常遇到的反复接触低剂量有机磷，虽不足以引发胆碱能危象，但也会给人们带来严重风险。例如，多项流行病学研究已确定职业性有机磷暴露与神经退行性疾病、精神疾病以及感觉运动功能障碍之间存在关联。要对这些流行病学发现背后的基础科学机制进行严谨的科学研究，就需要有效的临床前模型，在该模型中，严格调控的暴露模式可与神经毒性相关联。在此，我们综述了该领域目前使用的职业性有机磷暴露实验模型。我们发现，模拟职业性有机磷暴露的动物研究确实显示出神经毒性的证据，并且这些模型的应用有助于阐明有机磷诱导神经后遗症的潜在机制。尽管如此，仍有必要进一步开展工作，以评估暴露水平、防护方法和治疗策略，综合起来这些可用于修订全球改善工作场所条件的指导方针。
