Neurobiology Sector and IIT Unit, International School for Advanced Studies (SISSA), Via Bonomea 265, 34136 Trieste, Italy.
Neural Plast. 2011;2011:297153. doi: 10.1155/2011/297153. Epub 2011 Jun 23.
Autism spectrum disorders (ASDs) comprise a heterogeneous group of pathological conditions, mainly of genetic origin, characterized by stereotyped behavior, marked impairment in verbal and nonverbal communication, social skills, and cognition. Interestingly, in a small number of cases, ASDs are associated with single mutations in genes encoding for neuroligin-neurexin families. These are adhesion molecules which, by regulating transsynaptic signaling, contribute to maintain a proper excitatory/inhibitory (E/I) balance at the network level. Furthermore, GABA, the main inhibitory neurotransmitter in adult life, at late embryonic/early postnatal stages has been shown to depolarize and excite targeted cell through an outwardly directed flux of chloride. The depolarizing action of GABA and associated calcium influx regulate a variety of developmental processes from cell migration and differentiation to synapse formation. Here, we summarize recent data concerning the functional role of GABA in building up and refining neuronal circuits early in development and the molecular mechanisms regulating the E/I balance. A dysfunction of the GABAergic signaling early in development leads to a severe E/I unbalance in neuronal circuits, a condition that may account for some of the behavioral deficits observed in ASD patients.
自闭症谱系障碍（ASD）包括一组主要为遗传起源的异质性病理状况，其特征为刻板行为、言语和非言语交流、社交技能和认知方面的严重损伤。有趣的是，在少数情况下，ASD 与编码神经粘连蛋白-神经递质素家族的基因的单一突变有关。这些是黏附分子，通过调节突触间信号传递，有助于在网络水平上维持适当的兴奋/抑制（E/I）平衡。此外，在胚胎后期/出生后早期阶段，GABA（成年期的主要抑制性神经递质）已被证明通过氯离子的外向流动使靶细胞去极化并兴奋。GABA 的去极化作用和相关的钙内流调节了从细胞迁移和分化到突触形成等多种发育过程。在这里，我们总结了最近关于 GABA 在早期发育过程中构建和完善神经元回路的功能作用以及调节 E/I 平衡的分子机制的相关数据。早期发育过程中 GABA 能信号传递的功能障碍会导致神经元回路中严重的 E/I 失衡，这种情况可能解释了 ASD 患者观察到的一些行为缺陷的原因。
