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浙江大学学报（医学版）
浙江大学学报（医学版）  2017, Vol. 46 Issue (1): 22-29    DOI: 10.3785/j.issn.1008-9292.2017.02.04
癫痫的形成机制及其诊治专题     
颞叶癫痫与海马成体神经再生
陈立颖(),汪仪,陈忠()
浙江大学药学院, 浙江 杭州 310058
Temporal lobe epilepsy and adult hippocampal neurogenesis
CHEN Liying(),WANG Yi,CHEN Zhong()
College of Pharmacy, Zhejiang University, Hangzhou 310058, China
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摘要：

颞叶癫痫是一种严重的慢性中枢系统疾病，难治性比例非常高，它不仅会损害海马的结构功能，还会影响海马齿状回区的成体神经再生。颞叶癫痫模型研究表明，海马齿状回区的内源性神经干细胞在癫痫持续状态后会迅速激活，神经再生水平显著提高，而在癫痫发作后期（慢性期）神经元再生水平降低至正常水平以下；另外，癫痫持续状态后产生并分化成熟的颗粒细胞会存在异常的形态和位置，并有可能异常整合到海马神经环路并对癫痫的形成和发作产生影响。然而，癫痫后的成体神经再生对于癫痫是利是弊仍存在较大争议。本文对近年来颞叶癫痫后成体神经再生的数量、形态和功能的研究进展进行综述，讨论成体神经再生在癫痫形成和病理机制中扮演的角色，为日后临床上以成体神经再生作为癫痫治疗调控的新靶点研究提供借鉴。
关键词： 癫痫, 颞叶/病理生理学;  齿状回/病理学;  齿状回/解剖学和组织学;  癫痫持续状态;  神经元;  神经再生;  疾病模型, 动物;  综述    
Abstract:

Temporal lobe epilepsy (TLE) is a common and severe neurological disorder which is often intractable. It can not only damage the normal structure and function of hippocampus, but also affect the neurogenesis in dentate gyrus (DG). It is well documented from researches on the animal models of TLE that after a latent period of several days, prolonged seizure activity leads to a dramatic increase in mitotic activity in the hippocampal DG. However, cell proliferation returns to baseline levels within 3-4 weeks after status epilepticus (SE). Meanwhile, there are two major abnormalities of DG neurogenesis, including the formation of hilar basal dendrites and the ectopic migration of newborn granule cells into the polymorphic cell layer, which may affect epileptogenesis and seizure onset. However, the specific contribution of these abnormalities to seizures is still unknown. In other words, whether they are anti-epileptic or pro-epileptic is still under heated discussion. This article systematically reviews current knowledge on neurogenesis and epilepsy based on the results of studies in recent years and discusses the possible roles of neurogenesis in epileptogenesis and pathologic mechanisms, so as to provide information for the potential application of neurogenesis as a new clinical therapeutic target for temporal lobe epilepsy.
Key words: Epilepsy, temporal lobe/physiopathology    Dentate gyrus/pathology    Dentate gyrus/pathology/anatomy&histology    Status epilepticus    Neurons    Nerve regeneration    Disease models, animal    Review
收稿日期: 2016-10-02 出版日期: 2017-07-07
CLC:  R741.02  
基金资助: 浙江省卫生厅高层次人才培养工程;国家自然科学基金(91332202)
通讯作者: 陈忠     E-mail: chenliying0129@163.com;chenzhong@zju.edu.cn
作者简介: 陈立颖 (1993-), 女, 博士研究生, 主要从事癫痫的基础研究; E-mail: chenliying0129@163.com|陈忠 (1968-), 男, 博士, 教授, 博士生导师, 主要从事慢性脑病的分子生物学机制及药物新靶点研究. E-mail: chenzhong@zju.edu.cn
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引用本文:

陈立颖,汪仪,陈忠. 颞叶癫痫与海马成体神经再生[J]. 浙江大学学报（医学版）, 2017, 46(1): 22-29.

CHEN Liying,WANG Yi,CHEN Zhong. Temporal lobe epilepsy and adult hippocampal neurogenesis. J Zhejiang Univ (Med Sci), 2017, 46(1): 22-29.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2017.02.04    或    http://www.zjujournals.com/med/CN/Y2017/V46/I1/22

图1  海马内正常状态的成体神经再生和癫痫状态下的成体再生神经元发育成熟和功能整合 A：正常状态下海马齿状回区的放射状胶质细胞样前体细胞 (rNSC) 被激活后产生神经前体细胞，再分化成为不成熟神经元初步形成树突，然后成熟，树突延伸进入分子层，轴突经过门区延伸到CA3；B：癫痫持续状态后海马齿状回区rNSC被激活产生神经前体细胞，再分化成为不成熟神经元时不仅更早形成了正常的树突还在胞体底部形成了基底树突 (▲)。成熟后，神经元异常迁移离开颗粒细胞层在门区内向CA3迁移，部分轴突会反向伸展到达分子层，发生癫痫后常见的病理现象——苔藓纤维出芽 (△)，从而形成异常的兴奋性环路.DG:海马齿状回区；GCL：颗粒细胞层；ML:分子层.
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