{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T15:32:02Z","timestamp":1747150322532,"version":"3.40.5"},"reference-count":74,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T00:00:00Z","timestamp":1686268800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01NS117469","R21 DC016135"],"award-info":[{"award-number":["R01NS117469","R21 DC016135"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["1UL1TR002373"],"award-info":[{"award-number":["1UL1TR002373"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2023,12]]},"abstract":"<jats:sec><jats:title>Objectives and hypothesis<\/jats:title><jats:p>Vocal dysfunction, including hypophonia, in Parkinson disease (PD) manifests in the prodromal period and significantly impacts an individual's quality of life. Data from human studies suggest that pathology leading to vocal deficits may be structurally related to the larynx and its function. The <jats:italic>Pink1<\/jats:italic>\u2212\/\u2212 rat is a translational model used to study pathogenesis in the context of early\u2010stage mitochondrial dysfunction. The primary objective of this work was to identify differentially expressed genes in the thyroarytenoid muscle and examine the dysregulated biological pathways in the female rat.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RNA sequencing was used to determine thyroarytenoid (TA) muscle gene expression in adult female <jats:italic>Pink1<\/jats:italic>\u2212\/\u2212 rats compared with controls. A bioinformatic approach and the ENRICHR gene analysis tool were used to compare the sequencing dataset with biological pathways and processes, disease relationships, and drug\u2010repurposing compounds. Weighted Gene Co\u2010expression Network Analysis was used to construct biological network modules. The data were compared with a previously published dataset in male rats.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Significant upregulated pathways in female <jats:italic>Pink1<\/jats:italic>\u2212\/\u2212 rats included fatty acid oxidation and muscle contraction, synaptic transmission, and neuromuscular processes. Downregulated pathways included anterograde transsynaptic signaling, chemical synaptic transmission, and ion release. Several drug treatment options including cetuximab, fluoxetine, and resveratrol are hypothesized to reverse observed genetic dysregulation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Data presented here are useful for identifying biological pathways that may underlie the mechanisms of peripheral dysfunction including neuromuscular synaptic transmission to the TA muscle. These experimental biomarkers have the potential to be targeted as sites for improving the treatment for hypophonia in early\u2010stage PD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 133:3412\u20133421, 2023<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.30768","type":"journal-article","created":{"date-parts":[[2023,6,9]],"date-time":"2023-06-09T11:30:44Z","timestamp":1686310244000},"page":"3412-3421","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Thyroarytenoid Oxidative Metabolism and Synaptic Signaling Dysregulation in the Female <i>Pink1<\/i>\u2212\/\u2212 Rat"],"prefix":"10.1002","volume":"133","author":[{"given":"David G. 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