Local GDNF expression mediated by lentiviral vector protects facial nerve motoneurons but not spinal motoneurons in SOD1G93A transgenic mice

被引:38
作者
Guillot, S
Azzouz, M
Déglon, N
Zurn, A
Aebischer, P
机构
[1] Swiss Fed Inst Technol, Inst Neurosci, EPFL, CH-1015 Lausanne, Switzerland
[2] Oxford BioMed Ltd, Oxford, England
[3] Univ Lausanne, Sch Med, Dept Expt Surg, CH-1015 Lausanne, Switzerland
关键词
glial cell line-derived neurotrophic factor; lentiviral vector; amyotrophic lateral sclerosis;
D O I
10.1016/j.nbd.2004.01.017
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Approximately 2% of amyotrophic lateral sclerosis (ALS) cases are associated with mutations in the cytosolic Cu/Zn superoxide dismutase 1 (SOD1) gene. Transgenic SOD1 mice constitute useful models of ALS to screen therapeutical approaches. Glial cell line-derived neurotrophic factor (GDNF) holds promises for the treatment of motoneuron disease. In the present study, GDNF expression in motoneurons of SOD1(G93A) transgenic mice was assessed by facial nucleus or intraspinal injection of lentiviral vectors (LV) encoding GDNF. We show that lentiviral vectors allow the expression for at least 12 weeks of GDNF that was clearly detected in motoneurons. This robust intraspinal expression did, however, not prevent the loss of motoneurons and muscle denervation of transgenic mice. In contrast, LV-GDNF induced a significant rescue of motoneurons in the facial nucleus and prevented motoneuron atrophy. The differential effect of GDNF on facial nucleus versus spinal motoneurons suggests different vulnerability., of motoneurons in ALS. (C) 2004 Elsevier Inc. All rights reserved.
引用
收藏
页码:139 / 149
页数:11
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