Ciammola A, Sassone J, Cannella M, Calza S, Poletti B, Frati L, Squitieri F, Silani V
Department of Neurology and Laboratory of Neuroscience, Dino Ferrari Center, IRCCS Istituto Auxologico Italiano, Milan, Italy.
Am J Med Genet B Neuropsychiatr Genet. 2007 Jun 5;144B(4):574-7. doi: 10.1002/ajmg.b.30501.
Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms and by a progressive degeneration of neurons in basal ganglia and in brain cortex. Brain-derived neurotrophic factor (BDNF) is a pro-survival factor for striatal neurons. Some evidence implicates a brain BDNF deficiency, related to mutated huntingtin expression, in the selective vulnerability of striatal neurons in HD. We compared BDNF serum levels in 42 patients with HD (range 28-72 years, mean age 51.9 +/- 11.5), and 42 age-matched healthy subjects (range 25-68 years, mean age 48.2 +/- 12.5). We evaluated the potential relationship between BDNF serum levels, CAG repeat number (range 40-54, mean 44.8 +/- 3.4) and duration of illness (range 6-228 months, mean 103.6 +/- 62.1). Serum BDNF levels were significantly lower in patients than in age-matched healthy subjects. Lower BDNF levels were associated with a longer CAG repeat length and a longer duration of illness. Severity of the illness, as assessed by the Unified Huntington's Disease Rating Scale (UHDRS) motor and cognitive scores, was negatively related to serum BDNF levels. These results in vivo confirm that the huntingtin mutation causes BDNF production to decline and show that the BDNF deficiency is detectable in HD patients' sera. Further studies on a larger sample size should confirm whether BDNF concentrations in patients' serum could be a useful clinical marker related to the patients' disease phenotype.
亨廷顿舞蹈症（HD）是一种神经退行性疾病，其特征为运动、认知和精神症状，以及基底神经节和大脑皮层中神经元的进行性退化。脑源性神经营养因子（BDNF）是纹状体神经元的促存活因子。一些证据表明，与突变的亨廷顿蛋白表达相关的脑BDNF缺乏与HD中纹状体神经元的选择性易损性有关。我们比较了42例HD患者（年龄范围28 - 72岁，平均年龄51.9±11.5岁）和42例年龄匹配的健康受试者（年龄范围25 - 68岁，平均年龄48.2±12.5岁）的BDNF血清水平。我们评估了BDNF血清水平、CAG重复次数（范围40 - 54，平均44.8±3.4）与病程（范围6 - 228个月，平均103.6±62.1）之间的潜在关系。患者的血清BDNF水平显著低于年龄匹配的健康受试者。较低的BDNF水平与更长的CAG重复长度和更长的病程相关。通过统一亨廷顿舞蹈病评定量表（UHDRS）运动和认知评分评估的疾病严重程度与血清BDNF水平呈负相关。这些体内研究结果证实，亨廷顿蛋白突变导致BDNF产生下降，并表明HD患者血清中可检测到BDNF缺乏。对更大样本量的进一步研究应证实患者血清中的BDNF浓度是否可能是与患者疾病表型相关的有用临床标志物。
