Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons.
Nicotine Elicits Convulsive Seizures by Activating Amygdalar Neurons.
复制标题
DOI：
10.3389/fphar.2017.00057
复制
发表时间：
2017
影响因子：
5.6
通讯作者：
Ohno Y
中科院分区：
文献类型：
--
作者：
Iha HA;Kunisawa N;Shimizu S;Tokudome K;Mukai T;Kinboshi M;Ikeda A;Ito H;Serikawa T;Ohno Y
尼古丁乙酰胆碱（nACh）受体与癫痫疾病的发病机制有关；然而，nACh受体在癫痫发作中的作用机制尚不清楚。在这里，我们对小鼠和大鼠进行了行为和免疫组织化学研究，以阐明尼古丁诱发癫痫发作的机制。用尼古丁（1-4 mg/kg, i.p）治疗的动物以剂量依赖的方式产生运动兴奋，并引起3和4 mg/kg的惊厥发作。尼古丁引起的癫痫发作被一种亚型非选择性nACh拮抗剂甲胺（MEC）所消除。α7 nACh拮抗剂甲基莱卡乌碱也能显著抑制尼古丁诱导的癫痫发作，而α4β2 nACh拮抗剂二氢β-红血碱的作用较弱。神经兴奋的生物学标志物Fos蛋白表达的地形分析显示，抽搐剂量（4 mg/kg）尼古丁区域特异性激活了48个脑区中梨状皮质、杏仁核、内侧缰核、幕旁丘脑、下丘脑前部和孤立核的神经元，并且这也被MEC抑制。此外，杏仁核的电损伤，而不是梨状皮质、内侧缰核和丘脑，特异性地抑制尼古丁引起的癫痫发作。此外，在杏仁核中微量注射尼古丁（100和300 μg/侧）可引起惊厥发作，且呈剂量相关。目前的研究结果表明，尼古丁主要通过α7 nACh受体激活杏仁核神经元，从而引起惊厥发作。
Nicotinic acetylcholine (nACh) receptors are implicated in the pathogenesis of epileptic disorders; however, the mechanisms of nACh receptors in seizure generation remain unknown. Here, we performed behavioral and immunohistochemical studies in mice and rats to clarify the mechanisms underlying nicotine-induced seizures. Treatment of animals with nicotine (1–4 mg/kg, i.p.) produced motor excitement in a dose-dependent manner and elicited convulsive seizures at 3 and 4 mg/kg. The nicotine-induced seizures were abolished by a subtype non-selective nACh antagonist, mecamylamine (MEC). An α7 nACh antagonist, methyllycaconitine, also significantly inhibited nicotine-induced seizures whereas an α4β2 nACh antagonist, dihydro-β-erythroidine, affected only weakly. Topographical analysis of Fos protein expression, a biological marker of neural excitation, revealed that a convulsive dose (4 mg/kg) of nicotine region-specifically activated neurons in the piriform cortex, amygdala, medial habenula, paratenial thalamus, anterior hypothalamus and solitary nucleus among 48 brain regions examined, and this was also suppressed by MEC. In addition, electric lesioning of the amygdala, but not the piriform cortex, medial habenula and thalamus, specifically inhibited nicotine-induced seizures. Furthermore, microinjection of nicotine (100 and 300 μg/side) into the amygdala elicited convulsive seizures in a dose-related manner. The present results suggest that nicotine elicits convulsive seizures by activating amygdalar neurons mainly via α7 nACh receptors.