Schroeder Analyne M, Loh Dawn H, Jordan Maria C, Roos Kenneth P, Colwell Christopher S
Department of Psychiatry & Biobehavioral Sciences, Laboratory of Circadian and Sleep Medicine, University of California, Los Angeles, Los Angeles, CA, 90024 USA and Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095-1751.
PLoS Curr. 2011 Nov 4;3:RRN1266. doi: 10.1371/currents.RRN1266.
Huntington's disease is a progressive, neurodegenerative disorder that presents with a triad of clinical symptoms, which include movement abnormalities, emotional disturbance and cognitive impairment. Recent studies reported dysfunction of the autonomic nervous system in Huntington's disease patients, which may contribute to the increased incidence of cardiovascular events in this patient population that often leads to death. We measured the baroreceptor reflex, a process dependent on proper autonomic function, in the BACHD mouse model of Huntington's disease. We found a blunted response of the baroreceptor reflex as well as significantly higher daytime blood pressure in BACHD mice compared to WT controls, which are both indications of autonomic dysfunction. BACHD mice had increased heart weight to tibia length ratios at 7 and 12 mo of age suggesting hypertrophic changes of the heart, which we speculate is a response to the increased blood pressure and aberrant baroreceptor reflex. Despite these structural changes, the hearts of BACHD mice continue to function normally as assessed by echocardiographic analysis. Studies of autonomic and cardiovascular function in BACHD mice may help elucidate the pathophysiology of Huntington's disease and aid in the development of clinical strategies to offset the incidence of fatal cardiovascular events in the Huntington's disease patient population.
亨廷顿舞蹈症是一种进行性神经退行性疾病,其临床症状表现为三联征,包括运动异常、情绪障碍和认知障碍。最近的研究报告称,亨廷顿舞蹈症患者存在自主神经系统功能障碍,这可能是导致该患者群体心血管事件发生率增加并常导致死亡的原因。我们在亨廷顿舞蹈症的BACHD小鼠模型中测量了压力感受器反射,这一过程依赖于正常的自主神经功能。我们发现,与野生型对照相比,BACHD小鼠的压力感受器反射反应迟钝,白天血压也显著更高,这两者都是自主神经功能障碍的迹象。BACHD小鼠在7个月和12个月大时心脏重量与胫骨长度的比值增加,表明心脏发生了肥厚性变化,我们推测这是对血压升高和异常压力感受器反射的一种反应。尽管有这些结构变化,但通过超声心动图分析评估,BACHD小鼠的心脏仍能正常运作。对BACHD小鼠自主神经和心血管功能的研究可能有助于阐明亨廷顿舞蹈症的病理生理学,并有助于制定临床策略,以降低亨廷顿舞蹈症患者群体中致命心血管事件的发生率。