McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Curr Opin Neurobiol. 2018 Feb;48:59-63. doi: 10.1016/j.conb.2017.10.014. Epub 2017 Nov 7.
Developmental processes disrupted in neurodevelopmental disorders occur rapidly and with temporal precision. During development, individual gene activity can dynamically engage different signaling networks; thus genetic mutations can lead to different functional changes at different times. Interpretation of phenotypes can be further complicated if initial functional changes trigger compensatory mechanisms. Examining genetic mouse models of neurodevelopmental disorders reveals cellular phenotypes that change over the course of development and exist long before behavioral deficits are assessed. Correspondingly, earlier genetic interventions in these disorder models have often been more effective at improving behavioral deficits than late interventions. The restricted period of effective intervention demonstrates that identifying a target window is an essential component of treatment.
神经发育障碍中发育过程的紊乱发生得很快且具有时间准确性。在发育过程中,单个基因的活性可以动态地参与不同的信号网络;因此,基因突变可以在不同时间导致不同的功能变化。如果最初的功能变化引发补偿机制,那么对表型的解释可能会更加复杂。检查神经发育障碍的遗传小鼠模型揭示了在行为缺陷得到评估之前,随着时间的推移而发生变化的细胞表型。相应地,在这些疾病模型中早期的遗传干预通常比晚期干预更有效地改善行为缺陷。有效的干预时间有限,这表明确定目标窗口是治疗的一个重要组成部分。