Low brain-derived neurotrophic factor (BDNF) levels in serum of Huntington's disease patients

被引:132
作者
Ciammola, A.
Sassone, J.
Cannella, M.
Calza, S.
Poletti, B.
Frati, L.
Squitieri, F.
Silani, V.
机构
[1] IRCCS, Ist Auxol Italiano, Dept Neurol, I-20149 Milan, Italy
[2] IRCCS, Ist Auxol Italiano, Neurosci Lab, Dino Ferrari Ctr, I-20149 Milan, Italy
[3] IRCCS, Neuromed, Neurogenet Unit, Pozzilli, Isernia, Italy
[4] Univ Brescia, Dept Biomed Sci & Biotechnol, Brescia, Italy
[5] Univ Roma La Sapienza, Dept Expt Med & Pathol, Rome, Italy
[6] Univ Milan, Sch Med, Milan, Italy
关键词
BDNF; human serum; Huntington's disease;
D O I
10.1002/ajmg.b.30501
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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. (c) 2007 Wiley-Liss, Inc.
引用
收藏
页码:574 / 577
页数:4
相关论文
共 31 条
[1]   Anterograde transport of brain-derived neurotrophic factor and its role in the brain [J].
Altar, CA ;
Cai, N ;
Bliven, T ;
Juhasz, M ;
Conner, JM ;
Acheson, AL ;
Lindsay, RM ;
Wiegand, SJ .
NATURE, 1997, 389 (6653) :856-860
[2]   Cystamine and cysteamine increase brain levels of BDNF in Huntington disease via HSJ1b and transglutaminase [J].
Borrell-Pagès, M ;
Canals, JM ;
Cordelières, FP ;
Parker, JA ;
Pineda, JR ;
Grange, G ;
Bryson, EA ;
Guillermier, M ;
Hirsch, E ;
Hantraye, P ;
Cheetham, ME ;
Néri, C ;
Alberch, J ;
Brouillet, E ;
Saudou, F ;
Humbert, S .
JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (05) :1410-1424
[3]   Brain-derived neurotrophic factor regulates the onset and severity of motor dysfunction associated with enkephalinergic neuronal degeneration in Huntington's disease [J].
Canals, JM ;
Pineda, JR ;
Torres-Peraza, JF ;
Bosch, M ;
Martín-Ibañez, R ;
Muñoz, MT ;
Mengod, G ;
Ernfors, P ;
Alberch, J .
JOURNAL OF NEUROSCIENCE, 2004, 24 (35) :7727-7739
[4]  
Ciarmiello A, 2006, J NUCL MED, V47, P215
[5]   The role of neuronal growth factors in neurodegenerative disorders of the human brain [J].
Connor, B ;
Dragunow, M .
BRAIN RESEARCH REVIEWS, 1998, 27 (01) :1-39
[6]   Brain-derived neurotrophic factor in Huntington disease [J].
Ferrer, I ;
Goutan, E ;
Marín, C ;
Rey, MJ ;
Ribalta, T .
BRAIN RESEARCH, 2000, 866 (1-2) :257-261
[7]  
Fujimura H, 2002, THROMB HAEMOSTASIS, V87, P728
[8]   Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules [J].
Gauthier, LR ;
Charrin, BC ;
Borrell-Pagès, M ;
Dompierre, JP ;
Rangone, H ;
Cordelières, FP ;
De Mey, J ;
MacDonald, ME ;
Lessmann, V ;
Humbert, S ;
Saudou, F .
CELL, 2004, 118 (01) :127-138
[9]   Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients [J].
Gonul, AS ;
Akdeniz, F ;
Taneli, F ;
Donat, O ;
Eker, Ç ;
Vahip, S .
EUROPEAN ARCHIVES OF PSYCHIATRY AND CLINICAL NEUROSCIENCE, 2005, 255 (06) :381-386
[10]   Postnatal developmental profile of brain-derived neurotrophic factor in rat brain and platelets [J].
Karege, F ;
Schwald, M ;
Cisse, M .
NEUROSCIENCE LETTERS, 2002, 328 (03) :261-264