{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:40:30Z","timestamp":1790797230779,"version":"4.1.0"},"reference-count":58,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2012,9,28]],"date-time":"2012-09-28T00:00:00Z","timestamp":1348790400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2012,11,15]]},"abstract":"<jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>Heart disease has been attributed as a major cause of death in patients with Huntington's disease (HD). While little is known about cardiac complication(s) in HD, dysfunction of the autonomic nervous system (ANS) may play a role.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Using a mouse model of HD, we demonstrated that even from an early HD phase, there was enhanced sympathetic and parasympathetic nervous activities, leading to an unstable heart beat, various arrhythmias and, ultimately, sudden arrhythmic death.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Greater numbers of active neurons were found in brain regions important for autonomic regulation in HD mice, suggesting a centrally mediated mechanism that was underlying the ANS\u2010cardiac dysfunction.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our findings provide insight into a likely neurocardiac cause of death in HD, and warrant further clinical investigation.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p><jats:bold>Abstract\u2002<\/jats:bold> Huntington's disease (HD) is a heritable neurodegenerative disorder, with heart disease implicated as one major cause of death. While the responsible mechanism remains unknown, autonomic nervous system (ANS) dysfunction may play a role. We studied the cardiac phenotype in R6\/1 transgenic mice at early (3 months old) and advanced (7 months old) stages of HD. While exhibiting a modest reduction in cardiomyocyte diameter, R6\/1 mice had preserved baseline cardiac function. Conscious ECG telemetry revealed the absence of 24\u2010h variation of heart rate (HR), and higher HR levels than wild\u2010type littermates in young but not older R6\/1 mice. Older R6\/1 mice had increased plasma level of noradrenaline (NA), which was associated with reduced cardiac NA content. R6\/1 mice also had unstable R\u2013R intervals that were reversed following atropine treatment, suggesting parasympathetic nervous activation, and developed brady\u2010 and tachyarrhythmias, including paroxysmal atrial fibrillation and sudden death. c\u2010Fos immunohistochemistry revealed greater numbers of active neurons in ANS\u2010regulatory regions of R6\/1 brains. Collectively, R6\/1 mice exhibit profound ANS\u2010cardiac dysfunction involving both sympathetic and parasympathetic limbs, that may be related to altered central autonomic pathways and lead to cardiac arrhythmias and sudden death.<\/jats:p>","DOI":"10.1113\/jphysiol.2012.238113","type":"journal-article","created":{"date-parts":[[2012,8,14]],"date-time":"2012-08-14T03:24:36Z","timestamp":1344914676000},"page":"5845-5860","source":"Crossref","is-referenced-by-count":45,"title":["Neurocardiac dysregulation and neurogenic arrhythmias in a transgenic mouse model of Huntington's disease"],"prefix":"10.1113","volume":"590","author":[{"given":"Helen","family":"Kiriazis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole 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