Autism and Obsessive Compulsive Spectrum Program, Department of Psychiatry, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East 210th St, Bronx, New York 10467-2490;
Department of Neurobiology and Anatomy, University of Utah School of Medicine, 531A Wintrobe, 20N 1900 E, Salt Lake City, Utah 84132.
Curr Neuropharmacol. 2014 Jan;12(1):71-98. doi: 10.2174/1570159X113116660046.
Autism spectrum disorder (ASD) and Fragile X syndrome (FXS) are relatively common childhood neurodevelopmental disorders with increasing incidence in recent years. They are currently accepted as disorders of the synapse with alterations in different forms of synaptic communication and neuronal network connectivity. The major excitatory neurotransmitter system in brain, the glutamatergic system, is implicated in learning and memory, synaptic plasticity, neuronal development. While much attention is attributed to the role of metabotropic glutamate receptors in ASD and FXS, studies indicate that the ionotropic glutamate receptors (iGluRs) and their regulatory proteins are also altered in several brain regions. Role of iGluRs in the neurobiology of ASD and FXS is supported by a weight of evidence that ranges from human genetics to in vitro cultured neurons. In this review we will discuss clinical, molecular, cellular and functional changes in NMDA, AMPA and kainate receptors and the synaptic proteins that regulate them in the context of ASD and FXS. We will also discuss the significance for the development of translational biomarkers and treatments for the core symptoms of ASD and FXS.
自闭症谱系障碍（ASD）和脆性 X 综合征（FXS）是相对常见的儿童神经发育障碍，近年来发病率不断上升。它们目前被认为是突触疾病，存在不同形式的突触通讯和神经元网络连接改变。大脑中的主要兴奋性神经递质系统——谷氨酸能系统，与学习和记忆、突触可塑性、神经元发育有关。虽然代谢型谷氨酸受体（mGluRs）在 ASD 和 FXS 中的作用备受关注，但研究表明，离子型谷氨酸受体（iGluRs）及其调节蛋白在多个脑区也发生了改变。iGluRs 在 ASD 和 FXS 的神经生物学中的作用得到了广泛证据的支持，这些证据范围从人类遗传学到体外培养的神经元。在这篇综述中，我们将讨论 NMDA、AMPA 和 kainate 受体以及调节它们的突触蛋白在 ASD 和 FXS 中的临床、分子、细胞和功能变化。我们还将讨论开发 ASD 和 FXS 核心症状的转化生物标志物和治疗方法的意义。
