Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824, USA.
Neurotoxicology. 2012 Jan;33(1):119-26. doi: 10.1016/j.neuro.2011.12.014. Epub 2011 Dec 22.
Epilepsy or seizure disorder is one of the most common neurological diseases in humans. Although genetic mutations in ion channels and receptors and some other risk factors such as brain injury are linked to epileptogenesis, the underlying cause for the majority of epilepsy cases remains unknown. Gene-environment interactions are thought to play a critical role in the etiology of epilepsy. Exposure to environmental chemicals is an important risk factor. Methylmercury (MeHg) is a prominent environmental neurotoxicant, which targets primarily the central nervous system (CNS). Patients or animals with acute or chronic MeHg poisoning often display epileptic seizures or show increased susceptibility to seizures, suggesting that MeHg exposure may be associated with epileptogenesis. This mini-review highlights the effects of MeHg exposure, especially developmental exposure, on the susceptibility of humans and animals to seizures, and discusses the potential role of low level MeHg exposure in epileptogenesis. This review also proposes that a preferential effect of MeHg on the inhibitory GABAergic system, leading to disinhibition of excitatory glutamatergic function, may be one of the potential mechanisms underlying MeHg-induced changes in seizure susceptibility.
癫痫或癫痫发作障碍是人类最常见的神经疾病之一。尽管离子通道和受体的基因突变和一些其他风险因素,如脑损伤,与癫痫发生有关,但大多数癫痫病例的根本原因仍不清楚。基因-环境相互作用被认为在癫痫的发病机制中起着关键作用。暴露于环境化学物质是一个重要的危险因素。甲基汞(MeHg)是一种突出的环境神经毒素,主要针对中枢神经系统(CNS)。急性或慢性 MeHg 中毒的患者或动物常表现出癫痫发作或对癫痫发作的易感性增加,表明 MeHg 暴露可能与癫痫发生有关。这篇迷你综述强调了 MeHg 暴露,特别是发育暴露,对人类和动物对癫痫发作易感性的影响,并讨论了低水平 MeHg 暴露在癫痫发生中的潜在作用。本综述还提出,MeHg 对抑制性 GABA 能系统的优先作用,导致兴奋性谷氨酸能功能的去抑制,可能是 MeHg 引起的癫痫易感性变化的潜在机制之一。