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Glutamate mediated signaling in the pathophysiology of autism spectrum disorders

机译：谷氨酸介导的自闭症谱系疾病病理生理学中的信号传导

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Autism spectrum disorder (ASD) is a childhood neurodevelopmental disorder. During fetal and neonatal brain development, the cues for neurodevelopment are regulated in a well orchestrated manner. Generally, neurotransmitters play a major role in the formation of central nervous system (CNS) and peripheral nervous system (PNS). Glutamate, the excitatory neurotransmitter actively participates in various neurodevelopmental processes through complex regulatory events. Excitatory neurotransmitter signaling via glutamate receptors modulates cognitive functions such as memory and learning, which are usually impaired in ASD. Therefore, glutamate and its regulatory molecules are considered as potential targets for these disorders. Pharmacological, biochemical and behavioral studies reveal possible involvement of glutamatergic system in ASD pathology. An abnormal increase in electrical activity resulting from excessive glutamate signaling causes prolonged alterations in behavior, as commonly seen in ASDs. On the contrary, reports on animal models of hypoglutamatergia demonstrate phenotypes that overlap with features seen in autism. So controversies prevail whether to regard autism as hyper- or hypo-glutamatergic disorder. This paper reviews the role of glutamate and its regulatory proteins such as different receptors, transporters and metabolizing enzymes in the pathophysiology of ASD based on evidences gathered through multidisciplinary approaches. All these information raise the possibility of exploiting glutamatergic neurotransmitter system for future therapeutic interventions for ASD.
机译：自闭症谱系障碍（ASD）是儿童神经发育障碍。在胎儿和新生儿大脑发育过程中，神经发育的线索以良好的策划方式调节。通常，神经递质在形成中枢神经系统（CNS）和外周神经系统（PNS）中起主要作用。谷氨酸，兴奋性神经递质通过复杂的监管事件积极参与各种神经发育过程。通过谷氨酸受体的兴奋性神经递质信号传导调节诸如存储器和学习之类的认知功能，这些功能通常在ASD中受损。因此，谷氨酸及其调节分子被认为是这些疾病的潜在靶标。药理学，生化和行为研究揭示了谷氨酸谷物系统在ASD病理中的可能参与。由于谷氨酸发射过多导致谷氨酸信号传导产生的电活动的异常增加导致行为延长的改变，如ASDS常见。相反，有关吞咽抑制因素的动物模型的报道证明了与自闭症中观察到的特征重叠的表型。所以争议是普遍存在的是自闭症作为超级或多次谷胱甘肽障碍。本文综述了谷氨酸及其调节蛋白如不同的受体，转运蛋白和代谢酶在ASD的病理生理学中的作用，基于通过多学科方法收集的证据。所有这些信息都提出了利用谷胱甘肽神经递质系统的可能性，以便为ASD进行未来的治疗干预措施。

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