Lee Eun-Jae, Choi Su Yeon, Kim Eunjoon
Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
Department of Biological Sciences, KAIST, Daejeon 305-701, Republic of Korea.
Curr Opin Pharmacol. 2015 Feb;20:8-13. doi: 10.1016/j.coph.2014.10.007. Epub 2015 Jan 28.
Abnormalities and imbalances in neuronal excitatory and inhibitory synapses have been implicated in diverse neuropsychiatric disorders including autism spectrum disorders (ASDs). Increasing evidence indicates that dysfunction of NMDA receptors (NMDARs) at excitatory synapses is associated with ASDs. In support of this, human ASD-associated genetic variations are found in genes encoding NMDAR subunits. Pharmacological enhancement or suppression of NMDAR function ameliorates ASD symptoms in humans. Animal models of ASD display bidirectional NMDAR dysfunction, and correcting this deficit rescues ASD-like behaviors. These findings suggest that deviation of NMDAR function in either direction contributes to the development of ASDs, and that correcting NMDAR dysfunction has therapeutic potential for ASDs.
神经元兴奋性和抑制性突触的异常与失衡已被认为与包括自闭症谱系障碍（ASD）在内的多种神经精神疾病有关。越来越多的证据表明，兴奋性突触处N-甲基-D-天冬氨酸受体（NMDAR）功能障碍与ASD相关。与此相符的是，在编码NMDAR亚基的基因中发现了与人类ASD相关的基因变异。对NMDAR功能进行药理学增强或抑制可改善人类ASD症状。ASD动物模型表现出双向NMDAR功能障碍，纠正这种缺陷可挽救ASD样行为。这些发现表明，NMDAR功能向任何一个方向的偏离都有助于ASD的发展，并且纠正NMDAR功能障碍对ASD具有治疗潜力。
