Rett syndrome and neuronal development
Rett syndrome and neuronal development
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DOI：
10.1177/08830738050200091101
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发表时间：
2005-09-01
影响因子：
1.9
通讯作者：
Naidu, S
中科院分区：
文献类型：
--
作者：
Johnston, MV;Blue, ME;Naidu, S
Rett综合征的临床症状，以及神经病理学和脑成像，表明这种疾病破坏了神经元回路。使用受体放射自显影的研究表明，兴奋性谷氨酸和抑制性γ-氨基丁酸（GABA）突触受体的密度异常的年轻女性受试者与Rett综合征死后的大脑。MeCP 2是大多数患有Rett综合征的女性个体中异常的蛋白质，主要在神经元中表达，并在突触形成时的发育过程中出现。对Rett综合征患者鼻上皮的研究表明，嗅觉受体神经元的成熟在突触形成之前受到阻碍。最近的报告表明，MeCP 2控制脑源性神经营养因子和DNA结合同源框蛋白Dlx 5的表达。脑源性神经营养因子增强兴奋性突触处的谷氨酸神经传递，而Dlx 5在大多数GABA能神经元中表达并刺激GABA的合成。综上所述，这些信息支持了Rett综合征是突触发育的遗传性疾病的假设，特别是使用谷氨酸和GABA作为神经递质的突触。
The clinical signs of Rett syndrome, as well as neuropathology and brain imaging, suggest that the disorder disrupts neuronal circuits. Studies using receptor autoradiography demonstrate abnormalities in the density of excitatory glutamate and inhibitory gamma-aminobutyric acid (GABA) synaptic receptors in postmortem brain from young female subjects with Rett syndrome. MeCP2, the protein that is abnormal in most female individuals with Rett syndrome, is expressed predominantly in neurons and appears during development at the time of synapse formation. Studies of nasal epithelium from patients with Rett syndrome show that the maturation of olfactory receptor neurons is impeded prior to the time of synapse formation. Recent reports indicate that MeCP2 controls the expression of brain-derived neurotrophic factor and the DNA-binding homeobox protein Dlx5. Brain-derived neurotrophic factor enhances glutamate neurotransmission at excitatory synapses, whereas Dlx5 is expressed in most GABAergic neurons and stimulates the synthesis of GABA. Taken together, this information supports the hypothesis that Rett syndrome is a genetic disorder of synapse development, especially synapses that use glutamate and GABA as neurotransmitters.