Aberrant heart rate and brainstem brain-derived neurotrophic factor (BDNF) signaling in a mouse model of Huntington's disease

Kathleen J. Griffioen, Ruiqian Wan, Tashalee R. Brown, Eitan Okun, Simonetta Camandola, Mohamed R. Mughal, Terry M. Phillips, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Huntington's disease (HD) is associated with profound autonomic dysfunction including dysregulation of cardiovascular control often preceding cognitive or motor symptoms. Brain-derived neurotrophic factor (BDNF) levels are decreased in the brains of HD patients and HD mouse models, and restoring BDNF levels prevents neuronal loss and extends survival in HD mice. We reasoned that heart rate changes in HD may be associated with altered BDNF signaling in cardiovascular control nuclei in the brainstem. Here we show that heart rate is elevated in HD (N171-82Q) mice at presymptomatic and early disease stages, and heart rate responses to restraint stress are attenuated. BDNF levels were significantly reduced in brainstem regions containing cardiovascular nuclei in HD mice and human HD patients. Central administration of BDNF restored the heart rate to control levels. Our findings establish a link between diminished BDNF expression in brainstem cardiovascular nuclei and abnormal heart rates in HD mice, and suggest a novel therapeutic target for correcting cardiovascular dysfunction in HD.

Original languageEnglish (US)
JournalNeurobiology of Aging
Volume33
Issue number7
DOIs
StatePublished - Jul 2012
Externally publishedYes

Keywords

  • BDNF
  • Brainstem
  • Huntington's disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

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    Griffioen, K. J., Wan, R., Brown, T. R., Okun, E., Camandola, S., Mughal, M. R., Phillips, T. M., & Mattson, M. P. (2012). Aberrant heart rate and brainstem brain-derived neurotrophic factor (BDNF) signaling in a mouse model of Huntington's disease. Neurobiology of Aging, 33(7). https://doi.org/10.1016/j.neurobiolaging.2011.11.030