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Individuals with Rett syndrome, as well as rodent models of this disorder, demonstrate abnormal cortical responses to sound, which impair auditory discrimination ability. Vagus nerve stimulation (VNS) paired with tones has been shown to drive robust changes in the auditory cortex physiology of\n                    <jats:italic>Mecp2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    rats and has the potential to improve the communication abilities of individuals with Rett syndrome. The aim of this study was to describe the proteomic differences present in the auditory cortex of the\n                    <jats:italic>Mecp2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    rat model of Rett syndrome, as well as the molecular effect of VNS paired with tones. This study used global proteomic analysis of auditory cortex tissue taken from\n                    <jats:italic>Mecp2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    rats exposed to VNS paired with tones compared to untreated\n                    <jats:italic>Mecp2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    rats and wild\u2010type (WT) littermate controls with no VNS exposure. Our results demonstrate dysregulation of mitochondrial and synaptic proteins in the\n                    <jats:italic>Mecp2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    rat auditory cortex. In addition, we show that VNS\u2010tone pairing induces significant alterations to the auditory cortex proteome of\n                    <jats:italic>Mecp2<\/jats:italic>\n                    <jats:sup>+\/\u2212<\/jats:sup>\n                    rats by changing the expression of proteins involved in regulating synaptic vesicles and synaptic transmission. This work provides evidence of key mechanisms that may drive auditory processing dysfunction in Rett syndrome and demonstrates that VNS\u2010tone pairing is sufficient to alter protein expression in the auditory cortex.\n                  <\/jats:p>","DOI":"10.1002\/dneu.70032","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T05:26:46Z","timestamp":1777613206000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Vagus Nerve Stimulation Paired With Tones Alters the Auditory Cortex Proteome in a Rat Model of Rett Syndrome"],"prefix":"10.1002","volume":"86","author":[{"given":"Isabella K.","family":"Myers","sequence":"first","affiliation":[{"name":"Department of Neuroscience, School of Behavioral and Brain Sciences The University of Texas at Dallas  Richardson Texas USA"},{"name":"Texas Biomedical Device Center The University of Texas at Dallas  Richardson Texas 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