Johnston Michael, Blue Mary E, Naidu Sakkubai
Developmental Neuroscience Laboratory, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, USA; Department of Physical Medicine and Rehabilitation, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Developmental Neuroscience Laboratory, Kennedy Krieger Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
F1000Res. 2015 Dec 22;4. doi: 10.12688/f1000research.6987.1. eCollection 2015.
Rett syndrome is an extremely disabling X-linked nervous system disorder that mainly affects girls in early childhood and causes autism-like behavior, severe intellectual disability, seizures, sleep disturbances, autonomic instability, and other disorders due to mutations in the MeCP2 (methyl CpG-binding protein 2) transcription factor. The disorder targets synapses and synaptic plasticity and has been shown to disrupt the balance between glutamate excitatory synapses and GABAergic inhibitory synapses. In fact, it can be argued that Rett syndrome is primarily a disorder of synaptic plasticity and that agents that can correct this imbalance may have beneficial effects on brain development. This review briefly summarizes the link between disrupted synaptic plasticity mechanisms and Rett syndrome and early clinical trials that aim to target these abnormalities to improve the outcome for these severely disabled children.
瑞特综合征是一种极其致残的X连锁神经系统疾病，主要影响幼儿期女童，由于甲基化CpG结合蛋白2（MeCP2）转录因子发生突变，会导致类似自闭症的行为、严重智力残疾、癫痫发作、睡眠障碍、自主神经不稳定及其他病症。该疾病以突触和突触可塑性为靶点，并且已证实会破坏谷氨酸能兴奋性突触和γ-氨基丁酸能抑制性突触之间的平衡。事实上，可以说瑞特综合征主要是一种突触可塑性障碍，能够纠正这种失衡的药物可能对大脑发育具有有益作用。本综述简要总结了突触可塑性机制破坏与瑞特综合征之间的联系，以及旨在针对这些异常情况以改善这些严重残疾儿童预后的早期临床试验。
