| First Author | Kiriazis H | Year | 2012 |
| Journal | J Physiol | Volume | 590 |
| Issue | 22 | Pages | 5845-60 |
| PubMed ID | 22890713 | Mgi Jnum | J:203027 |
| Mgi Id | MGI:5523774 | Doi | 10.1113/jphysiol.2012.238113 |
| Citation | Kiriazis H, et al. (2012) Neurocardiac dysregulation and neurogenic arrhythmias in a transgenic mouse model of Huntington's disease. J Physiol 590(Pt 22):5845-60 |
| abstractText | 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-h variation of heart rate (HR), and higher HR levels than wild-type 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-R intervals that were reversed following atropine treatment, suggesting parasympathetic nervous activation, and developed brady- and tachyarrhythmias, including paroxysmal atrial fibrillation and sudden death. c-Fos immunohistochemistry revealed greater numbers of active neurons in ANS-regulatory regions of R6/1 brains. Collectively, R6/1 mice exhibit profound ANS-cardiac dysfunction involving both sympathetic and parasympathetic limbs, that may be related to altered central autonomic pathways and lead to cardiac arrhythmias and sudden death. |
