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

TitleAberrant heart rate and brainstem brain-derived neurotrophic factor (BDNF) signaling in a mouse model of Huntington's disease.
Publication TypeJournal Article
Year of Publication2012
AuthorsGriffioen KJ, Wan R, Brown TR, Okun E, Camandola S, Mughal MR, Phillips TM, Mattson MP
JournalNeurobiol Aging
Volume33
Issue7
Pagination1481.e1-5
Date Published2012 Jul
ISSN1558-1497
KeywordsAnimals, Brain Stem, Brain-Derived Neurotrophic Factor, Disease Models, Animal, Heart Rate, Humans, Huntington Disease, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Signal Transduction
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.

DOI10.1016/j.neurobiolaging.2011.11.030
Alternate JournalNeurobiol. Aging
PubMed ID22209255
PubMed Central IDPMC3329581
Grant ListZ01 AG000314-08 / NULL / Intramural NIH HHS / United States
ZIA AG000317-11 / NULL / Intramural NIH HHS / United States
ZIA AG000331-03 / NULL / Intramural NIH HHS / United States
ZIA AG000314-11 / NULL / Intramural NIH HHS / United States
ZIA AG000330-03 / NULL / Intramural NIH HHS / United States

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