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

被引：21

作者：

Griffioen, Kathleen J. ^{[1
]}

Wan, Ruiqian ^{[1
]}

Brown, Tashalee R. ^{[1
,2
]}

Okun, Eitan ^{[3
]}

Camandola, Simonetta ^{[1
]}

Mughal, Mohamed R. ^{[1
]}

Phillips, Terry M. ^{[4
]}

Mattson, Mark P. ^{[1
]}

机构：

[1] NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA

[2] Weill Cornell Rockefeller Sloan Kettering Triinst, New York, NY USA

[3] Bar Ilan Univ, Mina & Everard Goodman Fac Life Sci, IL-52900 Ramat Gan, Israel

[4] Natl Inst Biomed Imaging & Bioengn, Lab Bioengn & Phys Sci, NIH, Baltimore, MD USA

来源：

NEUROBIOLOGY OF AGING | 2012年 / 33卷 / 07期

关键词：

Huntington's disease; Brainstem; BDNF; STRESS; MICE; EXPRESSION; RECEPTOR;

D O I：

10.1016/j.neurobiolaging.2011.11.030

中图分类号：

R592 [老年病学]; C [社会科学总论];

学科分类号：

03 ; 0303 ; 100203 ;

摘要：

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. Published by Elsevier Inc.

引用

页码：1481.e1 / 1481.e5

页数：5

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