Ex vivo delivery of GDNF maintains motor function and prevents neuronal loss in a transgenic mouse model of Huntington's disease

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• 作者：Allison D. Ebert ; Amelia E. Barber ; Brittany M. Heins ; Clive N. Svendsen
• 关键词：Neural progenitor cells ; Transplantation ; Striatum ; Gene therapy
• 刊名：Experimental Neurology
• 出版年：2010
• 出版时间：July 2010
• 年：2010
• 卷：224
• 期：1
• 页码：155-162
• 全文大小：2367 K

文摘

Huntington's disease (HD) is an autosomal dominant disorder caused by expansion of polyglutamine repeats in the huntingtin gene leading to loss of striatal and cortical neurons followed by deficits in cognition and choreic movements. Growth factor delivery to the brain has shown promise in various models of neurodegenerative diseases, including HD, by reducing neuronal death and thus limiting motor impairment. Here we used mouse neural progenitor cells (mNPCs) as growth factor delivery vehicles in the N171-82Q transgenic mouse model of HD. mNPCs derived from the developing mouse striatum were isolated and infected with lentivirus expressing either glial cell line-derived neurotrophic factor (GDNF) or green fluorescent protein (GFP). Next, mNPCs^GDNF or mNPCs^GFP were transplanted bilaterally into the striatum of pre-symptomatic N171-82Q mice. We found that mNPCs^GDNF, but not mNPCs^GFP, maintained rotarod function and increased striatal neuron survival out to 3 months post-transplantation. Importantly, histological analysis showed GDNF expression through the duration of the experiment. Our data show that mNPCs^GDNF can survive transplantation, secrete GDNF for several weeks and are able to maintain motor function in this model of HD.