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

doi:10.1016/j.neurobiolaging.2011.11.030

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 journal › Article › peer-review

18 Scopus citations

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 language	English (US)
Journal	Neurobiology of Aging
Volume	33
Issue number	7
DOIs	https://doi.org/10.1016/j.neurobiolaging.2011.11.030
State	Published - Jul 2012
Externally published	Yes

Keywords

BDNF
Brainstem
Huntington's disease

ASJC Scopus subject areas

Clinical Neurology
General Neuroscience
Aging
Developmental Biology
Geriatrics and Gerontology

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10.1016/j.neurobiolaging.2011.11.030

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

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.",

keywords = "BDNF, Brainstem, Huntington's disease",

author = "Griffioen, {Kathleen J.} and Ruiqian Wan and Brown, {Tashalee R.} and Eitan Okun and Simonetta Camandola and Mughal, {Mohamed R.} and Phillips, {Terry M.} and Mattson, {Mark P.}",

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AU - Griffioen, Kathleen J.

AU - Wan, Ruiqian

AU - Brown, Tashalee R.

AU - Okun, Eitan

AU - Camandola, Simonetta

AU - Mughal, Mohamed R.

AU - Phillips, Terry M.

AU - Mattson, Mark P.

PY - 2012/7

Y1 - 2012/7

N2 - 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.

AB - 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.

KW - BDNF

KW - Brainstem

KW - Huntington's disease

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

Abstract

Keywords

ASJC Scopus subject areas

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