Fallah Merrick S, Eubanks James H
Division of Experimental and Translational Neuroscience, Krembil Research Institute, University Health Network, 399 Bathurst Street, Toronto, Ontario M5T 0S8, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Division of Experimental and Translational Neuroscience, Krembil Research Institute, University Health Network, 399 Bathurst Street, Toronto, Ontario M5T 0S8, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada; Department of Surgery (Neurosurgery), University of Toronto, Toronto, Ontario M5S 1A8, Canada.
Neuroscience. 2020 Oct 1;445:50-68. doi: 10.1016/j.neuroscience.2020.01.041. Epub 2020 Feb 12.
Genetic neurodevelopmental disorders - that often include epilepsy as part of their phenotype - are a heterogeneous and clinically challenging spectrum of disorders in children. Although seizures often contribute significantly to morbidity in these affected populations, the mechanisms of epileptogenesis in these conditions remain poorly understood. Different model systems have been developed to aid in unraveling these mechanisms, which include a number of specific mutant mouse lines which genocopy specific general types of mutations present in patients. These mouse models have not only allowed for assessments of behavioral and electrographic seizure phenotypes to be ascertained, but also have allowed effects on the neurodevelopmental alterations and cognitive impairments associated with these disorders to be examined. In addition, these models play a role in advancing our understanding of these epileptic processes and developing preclinical therapeutics. The concordance of seizure phenotypes - in a select group of rare, genetic, neurodevelopmental disorders and epileptic encephalopathies - found between human patients and their model counterparts will be summarized. This review aims to assess whether models of Rett syndrome, CDKL5 deficiency disorder, Fragile-X syndrome, Dravet syndrome, and Ohtahara syndrome phenocopy the seizures seen in human patients.
遗传性神经发育障碍——其表型通常包括癫痫——是儿童中一类异质性且在临床上具有挑战性的疾病谱。尽管癫痫发作在这些受影响人群的发病中常常起重要作用,但这些情况下癫痫发生的机制仍知之甚少。已开发出不同的模型系统来帮助阐明这些机制,其中包括一些特定的突变小鼠品系,它们基因复制了患者中存在的特定一般类型的突变。这些小鼠模型不仅能够确定行为和脑电图癫痫发作表型的评估,还能够研究对与这些疾病相关的神经发育改变和认知障碍的影响。此外,这些模型在增进我们对这些癫痫过程的理解以及开发临床前治疗方法方面发挥着作用。将总结在一小部分罕见的遗传性神经发育障碍和癫痫性脑病患者与其模型对应物之间发现的癫痫发作表型的一致性。本综述旨在评估雷特综合征、CDKL5缺乏症、脆性X综合征、德雷维特综合征和大田原综合征的模型是否模拟了人类患者中所见的癫痫发作。