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 HD brain, and restoring BDNF levels prevents neuronal loss and extends lifespan. We reasoned that heart rate changes in HD may be associated with altered BDNF signalling 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 and TrkB mRNA and protein levels were significantly decreased in brainstem cardiovascular nuclei in HD mice. 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: Huntington’s disease, brainstem, BDNF