Department of Physiology and Biophysics, University of Colorado Anschutz, Aurora, CO, USA.
Department of Integrative Biology, Oklahoma State University, Stillwater, OK, USA.
FASEB J. 2020 Mar;34(3):3501-3518. doi: 10.1096/fj.201902435R. Epub 2020 Feb 10.
Autism spectrum disorders (ASD) are strongly associated with auditory hypersensitivity or hyperacusis (difficulty tolerating sounds). Fragile X syndrome (FXS), the most common monogenetic cause of ASD, has emerged as a powerful gateway for exploring underlying mechanisms of hyperacusis and auditory dysfunction in ASD. This review discusses examples of disruption of the auditory pathways in FXS at molecular, synaptic, and circuit levels in animal models as well as in FXS individuals. These examples highlight the involvement of multiple mechanisms, from aberrant synaptic development and ion channel deregulation of auditory brainstem circuits, to impaired neuronal plasticity and network hyperexcitability in the auditory cortex. Though a relatively new area of research, recent discoveries have increased interest in auditory dysfunction and mechanisms underlying hyperacusis in this disorder. This rapidly growing body of data has yielded novel research directions addressing critical questions regarding the timing and possible outcomes of human therapies for auditory dysfunction in ASD.
自闭症谱系障碍（ASD）与听觉过敏或听觉过敏（难以忍受声音）密切相关。脆性 X 综合征（FXS）是 ASD 最常见的单基因病因，它为探索 ASD 中听觉过敏和听觉功能障碍的潜在机制提供了有力的途径。这篇综述讨论了在动物模型以及 FXS 个体中，FXS 中听觉通路在分子、突触和回路水平上的破坏的例子。这些例子突出了多种机制的参与，包括听觉脑干回路中突触发育异常和离子通道失调、神经元可塑性受损以及听觉皮层的网络过度兴奋。尽管这是一个相对较新的研究领域，但最近的发现增加了人们对这种疾病中听觉功能障碍和听觉过敏机制的兴趣。这一快速增长的数据为解决有关 ASD 中听觉功能障碍的人类治疗的时机和可能结果的关键问题提供了新的研究方向。
