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NMDA 受体和 AMPA 受体:发育与癫痫持续状态。

NMDA and AMPA receptors: development and status epilepticus.

机构信息

Institute of Physiology AS CR, Prague, Czech Republic.

出版信息

Physiol Res. 2013;62(Suppl 1):S21-38. doi: 10.33549/physiolres.932662.

DOI:10.33549/physiolres.932662
PMID:24329701
Abstract

Glutamate is the main excitatory neurotransmitter in the brain and ionotropic glutamate receptors mediate the majority of excitatory neurotransmission (Dingeldine et al. 1999). The high level of glutamatergic excitation allows the neonatal brain (the 2(nd) postnatal week in rat) to develop quickly but it also makes it highly prone to age-specific seizures that can cause lifelong neurological and cognitive disability (Haut et al. 2004). There are three types of ionotropic glutamate receptors (ligand-gated ion channels) named according to their prototypic agonists: N-methyl-D-aspartate (NMDA), 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl) propanoic acid (AMPA) and kainate (KA). During early stages of postnatal development glutamate receptors of NMDA and AMPA type undergo intensive functional changes owing to modifications in their subunit composition (Carter et al. 1988, Watanabe et al. 1992, Monyer et al. 1994, Wenzel et al. 1997, Sun et al. 1998, Lilliu et al. 2001, Kumar et al. 2002, Matsuda et al. 2002, Wee et al. 2008, Henson et al. 2010, Pachernegg et al. 2012, Paoletti et al. 2013). Participation and role of these receptors in mechanisms of seizures and epilepsy became one of the main targets of intensive investigation (De Sarro et al. 2005, Di Maio et al. 2012, Rektor 2013). LiCl/Pilocarpine (LiCl/Pilo) induced status epilepticus is a model of severe seizures resulting in development temporal lobe epilepsy (TLE). This review will consider developmental changes and contribution of NMDA and AMPA receptors in LiCl/Pilo model of status epilepticus in immature rats.

摘要

谷氨酸是大脑中的主要兴奋性神经递质,离子型谷氨酸受体介导大多数兴奋性神经递质传递(Dingeldine 等人,1999 年)。高浓度的谷氨酸能兴奋使新生大脑(大鼠出生后的第 2 周)能够快速发育,但也使其极易发生特定于年龄的癫痫发作,从而导致终身神经和认知障碍(Haut 等人,2004 年)。有三种类型的离子型谷氨酸受体(配体门控离子通道)根据其原型激动剂命名:N-甲基-D-天冬氨酸(NMDA)、2-氨基-3-(3-羟基-5-甲基异恶唑-4-基)丙酸(AMPA)和红藻氨酸(KA)。在出生后发育的早期阶段,由于亚基组成的改变,NMDA 和 AMPA 型谷氨酸受体经历了强烈的功能变化(Carter 等人,1988 年,Watanabe 等人,1992 年,Monyer 等人,1994 年,Wenzel 等人,1997 年,Sun 等人,1998 年,Lilliu 等人,2001 年,Kumar 等人,2002 年,Matsuda 等人,2002 年,Wee 等人,2008 年,Henson 等人,2010 年,Pachernegg 等人,2012 年,Paoletti 等人,2013 年)。这些受体在癫痫发作和癫痫机制中的参与和作用成为密集研究的主要目标之一(De Sarro 等人,2005 年,Di Maio 等人,2012 年,Rektor 2013 年)。氯化锂/毛果芸香碱(LiCl/Pilo)诱导的癫痫持续状态是一种严重癫痫发作的模型,导致颞叶癫痫(TLE)的发展。本综述将考虑 NMDA 和 AMPA 受体在未成熟大鼠 LiCl/Pilo 癫痫持续状态模型中的发育变化和贡献。

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