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通过对肌张力障碍小鼠模型发声的频谱分析来模拟喉肌张力障碍

Modeling Laryngeal Dystonia through Spectral Analyses of Vocalizations in a Dystonia Mouse Model.

作者信息

Fitzgerald Austin L, Coello Jonathan A, Lyon Alyssa M, Dao Breanne L, van der Heijden Meike E

机构信息

Fralin Biomedical Research Institute at Virginia Tech Carilion School of Medicine.

Translational Biology, Medicine, and Health, Virginia Polytechnic Institute and State University.

出版信息

bioRxiv. 2025 Jul 10:2025.07.07.663183. doi: 10.1101/2025.07.07.663183.

Abstract

Laryngeal dystonia is a task-specific, focal dystonia that disrupts vocal-motor control and significantly alters quality of life through impaired communication. Despite its early onset in many hereditary dystonias, effective treatments remain limited, in part due to the lack of a preclinical model that captures its circuit-level pathophysiology. Our experiment evaluates ultrasonic vocalizations (USVs) in ; mice, a cerebellum-specific generalized dystonia model, to assess translational relevance for laryngeal dystonia. At postnatal day 9, mutant mice demonstrated statistically significant reductions in total USV count, relative count of complex calls, and key spectral parameters-especially frequency modulation and power-mirroring phonatory abnormalities seen in human patients. Cluster analyses further revealed impaired vocal burst initiation, suggesting disrupted cerebellar coordination of temporal vocal-motor output. These findings support the model's construct and face validity for cerebellar contributions to disordered phonation. By revealing these potential translational biomarkers, our study establishes a foundational platform for future mechanistic and interventional research in laryngeal dystonia.

摘要

喉肌张力障碍是一种特定任务的局灶性肌张力障碍,它会干扰发声运动控制,并通过受损的沟通能力显著改变生活质量。尽管在许多遗传性肌张力障碍中其发病较早,但有效的治疗方法仍然有限,部分原因是缺乏能够捕捉其回路水平病理生理学的临床前模型。我们的实验评估了特定于小脑的全身性肌张力障碍模型小鼠的超声发声(USV),以评估其与喉肌张力障碍的转化相关性。在出生后第9天,突变小鼠的总USV计数、复杂叫声的相对计数以及关键频谱参数(特别是频率调制和功率)出现了统计学上的显著降低,这反映了人类患者中出现的发声异常。聚类分析进一步揭示了发声爆发起始受损,表明小脑对发声运动输出时间的协调受到破坏。这些发现支持了该模型对于小脑在发声障碍中所起作用的构建和表面效度。通过揭示这些潜在的转化生物标志物,我们的研究为未来喉肌张力障碍的机制和干预研究建立了一个基础平台。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/de5a/12265613/6466e1b34def/nihpp-2025.07.07.663183v1-f0001.jpg

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