Ex vivo delivery of GDNF maintains motor function and prevents neuronal loss in a transgenic mouse model of Huntington's disease. Exp Neurol 2010 Jul;224(1):155-62
Date
03/17/2010Pubmed ID
20227407DOI
10.1016/j.expneurol.2010.03.005Scopus ID
2-s2.0-77953701829 (requires institutional sign-in at Scopus site) 74 CitationsAbstract
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 3months 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.
Author List
Ebert AD, Barber AE, Heins BM, Svendsen CNAuthor
Allison D. Ebert PhD Associate Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Analysis of VarianceAnimals
Body Weight
Cell Count
Cells, Cultured
Corpus Striatum
Disease Models, Animal
Dopamine
Genetic Therapy
Genetic Vectors
Glial Cell Line-Derived Neurotrophic Factor
Huntington Disease
Immunohistochemistry
Lentivirus
Mice
Mice, Transgenic
Microscopy, Confocal
Motor Activity
Nerve Degeneration
Neurons
Rotarod Performance Test
Stem Cell Transplantation
