The multifaceted role of inhibition in epilepsy: seizure-genesis through excessive GABAergic inhibition in autosomal dominant nocturnal frontal lobe epilepsy
The multifaceted role of inhibition in epilepsy: seizure-genesis through excessive GABAergic inhibition in autosomal dominant nocturnal frontal lobe epilepsy
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DOI：
10.1097/wco.0b013e3282f52f5f
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发表时间：
2008-04-01
影响因子：
4.8
通讯作者：
Mody, Istvan
中科院分区：
文献类型：
--
作者：
Mann, Edward O.;Mody, Istvan
综述的目的虽然癫痫描述了一系列不同的综合征，传统的观点是，有一个共同的潜在的失败的能力，GABA能抑制克服过度的突触兴奋。这篇综述探讨了增强GABA能抑制的可能性，在新皮层也可能proepileptogenic.Recent findingsRecently，两个小鼠品系携带突变等位基因的α 4亚基的烟碱乙酰胆碱受体，与常染色体显性夜间额叶癫痫已被发现显示自发性癫痫发作。体外新皮质锥体神经元的记录显示，常染色体显性夜间额叶癫痫突变与尼古丁诱发的GABA能抑制的大量选择性增加相关，这可能是癫痫发生的关键因素，因为体内癫痫发作可被亚惊厥剂量的GABA（A）受体拮抗剂阻断，在常染色体显性夜间额叶癫痫小鼠中观察到的新皮层抑制的获得和癫痫发作的发展之间的精确联系仍然未知。然而，最近对皮层GABA能回路功能特性的了解表明，有几种可能的途径有待探索，这些途径的阐明可以使选择性治疗干预成为可能。
Purpose of reviewWhile epilepsy describes a heterogeneous array of syndromes, the conventional view is that there is a common underlying failure in the ability of GABAergic inhibition to overcome excessive synaptic excitation. This review explores the possibility that enhanced GABAergic inhibition in the neocortex could also be proepileptogenic.Recent findingsRecently, two mouse strains carrying mutant alleles of the alpha 4 subunit of the nicotinic acetylcholine receptor that are associated with autosomal dominant nocturnal frontal lobe epilepsy have been found to show spontaneous seizures. Recordings from neocortical pyramidal neurons in vitro show that the autosomal dominant nocturnal frontal lobe epilepsy mutations are associated with large selective increases in nicotine-evoked GABAergic inhibition, which may be key factor in epileptogenesis, as the seizures in vivo are blocked by subconvulsive doses of the GABA(A) receptor antagonist, picrotoxin.SummaryThe precise links between the observed gain of neocortical inhibition and development of seizures in autosomal dominant nocturnal frontal lobe epilepsy mice remain unknown. Recent insights into the functional properties of cortical GABAergic circuits, however, suggest several possible pathways to be explored, whose elucidation could enable selective therapeutic interventions.