Columbia University Vagelos College of Physicians and Surgeons, 630 W 168(th) St, New York, NY, 10032, USA.
Department of Pediatrics, Morgan Stanley Children's Hospital, Columbia University Medical Center, 620 W 168(th) St, New York, NY, 10032, USA.
Pharmacol Res. 2018 Jun;132:1-6. doi: 10.1016/j.phrs.2018.03.020. Epub 2018 Mar 31.
Autism-spectrum disorder (ASD) is a neurodevelopmental disorder characterized by persistent deficits in social communication and repetitive patterns of behavior. ASD is, however, often associated with medical comorbidities and gastrointestinal (GI) dysfunction is among the most common. Studies have demonstrated a correlation between GI dysfunction and the degree of social impairment in ASD. The etiology of GI abnormalities in ASD is unclear, though the association between GI dysfunction and ASD-associated behaviors suggest that overlapping developmental defects in the brain and the intestine and/or a defect in communication between the enteric and central nervous systems (ENS and CNS, respectively), known as the gut-brain axis, could be responsible for the observed phenotypes. Brain-gut abnormalities have been increasingly implicated in several disease processes, including ASD. As a critical modulator of ENS and CNS development and function, serotonin may be a nexus for the gut-brain axis in ASD. This paper reviews the role of serotonin in ASD from the perspective of the ENS. A murine model that has been demonstrated to possess brain, behavioral and GI abnormalities mimicking those seen in ASD harbors the most common serotonin transporter (SERT) based mutation (SERT Ala56) found in children with ASD. Discussion of the gut-brain manifestations in the SERT Ala56 mice, and their correction with developmental administration of a 5-HT agonist, are also addressed in conjunction with other future directions for diagnosis and treatment.
自闭症谱系障碍（ASD）是一种神经发育障碍，其特征是社会交往持续存在缺陷和行为重复模式。然而，ASD 通常与医学合并症有关，胃肠道（GI）功能障碍是最常见的合并症之一。研究表明，GI 功能障碍与 ASD 中的社交障碍程度之间存在相关性。ASD 中 GI 异常的病因尚不清楚，尽管 GI 功能障碍与 ASD 相关行为之间的关联表明，大脑和肠道之间重叠的发育缺陷和/或肠神经系统（ENS）和中枢神经系统（CNS）之间的通讯缺陷（分别为肠-脑轴）可能是导致观察到的表型的原因。脑-肠异常与包括 ASD 在内的几种疾病过程的关系越来越密切。作为 ENS 和 CNS 发育和功能的关键调节剂，血清素可能是 ASD 中肠-脑轴的枢纽。本文从 ENS 的角度综述了血清素在 ASD 中的作用。已经证明具有模拟 ASD 中所见的大脑、行为和 GI 异常的小鼠模型，携带有 ASD 儿童中最常见的血清素转运蛋白（SERT）基于突变（SERT Ala56）。还讨论了 SERT Ala56 小鼠中的肠-脑表现，以及用 5-HT 激动剂进行发育性给药对其的纠正，同时还讨论了其他未来的诊断和治疗方向。
