Synaptic determinants of rett syndrome.
Synaptic determinants of rett syndrome.
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DOI：
10.3389/fnsyn.2010.00028
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发表时间：
2010
影响因子：
3.7
通讯作者：
Giustetto M
中科院分区：
文献类型：
--
作者：
Boggio EM;Lonetti G;Pizzorusso T;Giustetto M
越来越多的证据表明，突触连接的结构和分子组织在人类患者以及神经和精神疾病的动物模型中都受到影响。作为这些实验观察的结果，人们引入了突触病的概念，这是一个描述大脑突触功能和可塑性疾病的概念。神经系统疾病和突触异常之间的密切相关性与这些综合征尤其相关，其中还包括其症状中的精神发育迟滞，例如雷特综合征（RS）。 RS (MIM312750) 是一种 X 连锁显性神经系统疾病，在大多数情况下是由甲基 CpG 结合蛋白 2 (MeCP2) 突变引起的。本综述将重点关注 RS 小鼠模型中 MeCP2 基因突变产生的突触改变的当前知识，并将重点介绍当前使用的实验疗法的前景。不同的实验方法表明，RS 可能是特定大脑区域突触传递稳态受损的结果。事实上，在缺乏 MeCP2 的情况下，经验诱导的神经元可塑性的几种形式都会受到损害。根据本综述中提出的结果，我们有理由认为，了解 RS 等疾病如何影响大脑是可以实现的。这项努力将使我们更接近于确定人类认知的神经生物学基础。
There is mounting evidence showing that the structural and molecular organization of synaptic connections is affected both in human patients and in animal models of neurological and psychiatric diseases. As a consequence of these experimental observations, it has been introduced the concept of synapsopathies, a notion describing brain disorders of synaptic function and plasticity. A close correlation between neurological diseases and synaptic abnormalities is especially relevant for those syndromes including also mental retardation in their symptomatology, such as Rett syndrome (RS). RS (MIM312750) is an X-linked dominant neurological disorder that is caused in the majority of cases by mutations in methyl-CpG-binding protein 2 (MeCP2). This review will focus on the current knowledge of the synaptic alterations produced by mutations of the gene MeCP2 in mouse models of RS and will highlight prospects experimental therapies currently in use. Different experimental approaches have revealed that RS could be the consequence of an impairment in the homeostasis of synaptic transmission in specific brain regions. Indeed, several forms of experience-induced neuronal plasticity are impaired in the absence of MeCP2. Based on the results presented in this review, it is reasonable to propose that understanding how the brain is affected by diseases such as RS is at reach. This effort will bring us closer to identify the neurobiological bases of human cognition.