Aberrant heart rate and brainstem brain-derived neurotrophic factor (BDNF) signaling in a mouse model of Huntington's disease
Aberrant heart rate and brainstem brain-derived neurotrophic factor (BDNF) signaling in a mouse model of Huntington's disease
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DOI：
10.1016/j.neurobiolaging.2011.11.030
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发表时间：
2012-07-01
影响因子：
4.2
通讯作者：
Mattson, Mark P.
中科院分区：
文献类型：
--
作者：
Griffioen, Kathleen J.;Wan, Ruiqian;Mattson, Mark P.
亨廷顿氏病（HD）与严重的自主神经功能障碍相关，包括心血管控制失调，通常在认知或运动症状之前。脑源性神经营养因子（BDNF）水平在HD患者和HD小鼠模型的大脑中降低，恢复BDNF水平可防止神经元丢失并延长HD小鼠的存活期。我们推测HD患者的心率变化可能与脑干心血管控制核团中BDNF信号的改变有关。在这里，我们表明，心率升高HD（N171- 82 Q）小鼠在症状前和疾病的早期阶段，和心率反应的约束压力减弱。在HD小鼠和人类HD患者中，含有心血管核团的脑干区域的BDNF水平显著降低。BDNF的中枢给药使心率恢复到对照水平。我们的研究结果建立了脑干心血管核团中BDNF表达减少与HD小鼠心率异常之间的联系，并提出了一种纠正HD心血管功能障碍的新治疗靶点。爱思唯尔公司出版
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.