Patel Jheel, Lukkes Jodi L, Shekhar Anantha
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States; Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research Institute, Indianapolis, IN, United States.
Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, United States.
Prog Brain Res. 2018;241:1-36. doi: 10.1016/bs.pbr.2018.10.002. Epub 2018 Nov 7.
Autism spectrum disorders (ASDs) are a group of neurodevelopment disorders that are characterized by heterogenous cognitive deficits and genetic factors. As more ASD risk genes are identified, genetic animal models have been developed to parse out the underlying neurobiological mechanisms of ASD. In this review, we discuss a subset of genetic models of ASD, focusing on those that have been widely studied and strongly linked to ASD. We focus our discussion of these models in the context of the theories and potential mechanisms of ASD, including disruptions in cell growth and proliferation, spine dynamics, synaptic transmission, excitation/inhibition balance, intracellular signaling, neuroinflammation, and behavior. In addition to ASD pathophysiology, we examine the limitations and challenges that genetic models pose for the study of ASD biology. We end with a review of innovative techniques and concepts of ASD pathology that can be further applied to and studied using genetic ASD models.
自闭症谱系障碍（ASD）是一组神经发育障碍，其特征是存在异质性认知缺陷和遗传因素。随着越来越多的ASD风险基因被识别出来，人们开发了遗传动物模型来剖析ASD潜在的神经生物学机制。在本综述中，我们讨论了ASD遗传模型的一个子集，重点关注那些已被广泛研究且与ASD有紧密联系的模型。我们在ASD的理论和潜在机制背景下讨论这些模型，包括细胞生长和增殖、树突棘动态、突触传递、兴奋/抑制平衡、细胞内信号传导、神经炎症和行为等方面的破坏。除了ASD病理生理学，我们还研究了遗传模型在ASD生物学研究中存在的局限性和挑战。最后，我们综述了ASD病理学的创新技术和概念，这些技术和概念可进一步应用于遗传ASD模型并利用其进行研究。
