TRPV1: A potential target for antiepileptogenesis
TRPV1: A potential target for antiepileptogenesis
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DOI：
10.1016/j.mehy.2009.01.005
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发表时间：
2009-07-01
影响因子：
4.7
通讯作者：
Zuo, Huancong
中科院分区：
文献类型：
--
作者：
Fu, Min;Xie, Zuoping;Zuo, Huancong
癫痫是神经科最常见的疾病之一。它是由中枢神经系统内兴奋和抑制的正常平衡受到多种不同的干扰而引起的。目前临床抗癫痫药物的作用靶点包括离子通道、神经递质转运体和神经递质代谢酶。他们可以控制大约70-80%的患者症状；20-30%的患者发展为顽固性癫痫患者。此外，抗癫痫药物不能阻止病灶的形成和疾病进程，而只能减轻癫痫发作的症状，并有因大剂量而产生不同不良影响的风险。最近。关于瞬时受体电位香草样受体1 （TRPV1）作用的令人印象深刻的数据证明它是一个鼓舞人心的抗癫痫靶点。TRPV1激活调节活动依赖的突触效能：(i)促进海马神经元的长期增强（LTP）和抑制长期抑制（LTD）； （ii）选择性抑制海马中间神经元上的兴奋性突触，这有望增加神经支配的锥体细胞的兴奋性。神经生长因子（NGF）可急性和慢性上调TRPV1的表达，提示TRPV1通道在NGF调控的癫痫发生过程中发挥重要作用。内源性大麻素（Endocannabinoid anandamide， AEA）是TRPV1内源性激动剂之一。已经证明，在癫痫过程中，AEA水平由于增强形成而增加，外源性给药和内源性产生的AEA都显示出前惊厥活性。此外，TRPV1激活会触发大鼠皮层培养物的凋亡神经元死亡，这可能是慢性癫痫中新皮层体积损失的原因，至少部分原因是。我们的假设可能会拓宽药物筛选和设计癫痫治疗的临床策略。2009爱思唯尔有限公司版权所有。
Epilepsy is one of the most common diseases in neurology department. It is caused by many different kinds of perturbances of normal balance of excitation and inhibition within the central nervous system. Current clinical antiepileptic drugs (AEDs) targets include ion channels, neurotransmitter transporters and neurotransmitter metabolic enzymes. They could control about 70-80% of the patients' symptoms; 20-30% patients develop to be intractable epilepsy sufferers. Moreover, antiepileptic drugs could not prevent formation of foci and disease process, but only alleviate symptoms of seizures at risk of different adverse effects as the consequences of large doses. Recently. impressive data on the actions of transient receptor potential vanilloid receptor 1 (TRPV1) prove it to be an inspiring antiepileptogenic target. TRPV1 activation modulates activity-dependent synaptic efficacy: (i) facilitating long-term potentiation (LTP) and suppressing long-term depression (LTD) of hippocampal neurons (ii) selectively inhibiting excitatory synapses onto hippocampal interneurons, which is expected to increase the excitability of innervated pyramidal cells. Nerve growth factor (NGF) can acutely and chronically upregulates TRPV1 expression, suggesting that TRPV1 channels would play an important role in the course of NGF regulated epileptogenesis. Endocannabinoid anandamide (AEA) is one of the TRPV1 endogenous agonists. It has been proved that, in the course of epilepsy, AEA levels increases due to enhanced formation and both exogenously administered and endogenously produced AEA display proconvulsant activity. Moreover, TRPV1 activation triggers apoptotic neuronal death of rat cortical cultures, which may be responsible, at least in part, for the volume loss of neocortex in chronic epilepsy. Our hypothesis may broaden the drug screening and designing for clinical strategies for epilepsy treatment. (C) 2009 Elsevier Ltd. All rights reserved.