Laboratory of Neurophysiology and Plasticity, IRCCS Fondazione Santa Lucia, Via del Fosso di Fiorano 64, 00143 Rome, Italy.
Department of Biology and Biotechnology "Charles Darwin", Sapienza University of Rome, P.le A. Moro 5, 00185 Rome, Italy.
Neurobiol Dis. 2022 Jan;162:105564. doi: 10.1016/j.nbd.2021.105564. Epub 2021 Nov 24.
This review provides an overview of the synaptic dysfunction of neuronal circuits and the ensuing behavioral alterations caused by mutations in autism spectrum disorder (ASD)-linked genes directly or indirectly affecting the postsynaptic neuronal compartment. There are plenty of ASD risk genes, that may be broadly grouped into those involved in gene expression regulation (epigenetic regulation and transcription) and genes regulating synaptic activity (neural communication and neurotransmission). Notably, the effects mediated by ASD-associated genes can vary extensively depending on the developmental time and/or subcellular site of expression. Therefore, in order to gain a better understanding of the mechanisms of disruptions in postsynaptic function, an effort to better model ASD in experimental animals is required to improve standardization and increase reproducibility within and among studies. Such an effort holds promise to provide deeper insight into the development of these disorders and to improve the translational value of preclinical studies.
本综述概述了自闭症谱系障碍(ASD)相关基因突变直接或间接影响突触后神经元区室导致的神经元回路突触功能障碍和随之而来的行为改变。有许多 ASD 风险基因,可大致分为参与基因表达调控(表观遗传调控和转录)和调节突触活性的基因(神经通讯和神经递质传递)。值得注意的是,由 ASD 相关基因介导的影响可能因表达的发育时间和/或亚细胞部位而广泛变化。因此,为了更好地理解突触后功能障碍的机制,需要在实验动物中更好地模拟 ASD,以提高研究内和研究间的标准化和重现性。这一努力有望更深入地了解这些疾病的发展,并提高临床前研究的转化价值。