Tags

Type your tag names separated by a space and hit enter

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.EN

Abstract

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.

Authors+Show Affiliations

Stem Cell and Regenerative Medicine Center, University of Wisconsin-Madison, 1111 Highland Ave., Madison, WI 53705, USA. aebert@wisc.eduNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20227407

Citation

Ebert, Allison D., et al. "Ex Vivo Delivery of GDNF Maintains Motor Function and Prevents Neuronal Loss in a Transgenic Mouse Model of Huntington's Disease." Experimental Neurology, vol. 224, no. 1, 2010, pp. 155-62.
Ebert AD, Barber AE, Heins BM, et al. Ex vivo delivery of GDNF maintains motor function and prevents neuronal loss in a transgenic mouse model of Huntington's disease. Exp Neurol. 2010;224(1):155-62.
Ebert, A. D., Barber, A. E., Heins, B. M., & Svendsen, C. N. (2010). Ex vivo delivery of GDNF maintains motor function and prevents neuronal loss in a transgenic mouse model of Huntington's disease. Experimental Neurology, 224(1), 155-62. https://doi.org/10.1016/j.expneurol.2010.03.005
Ebert AD, et al. Ex Vivo Delivery of GDNF Maintains Motor Function and Prevents Neuronal Loss in a Transgenic Mouse Model of Huntington's Disease. Exp Neurol. 2010;224(1):155-62. PubMed PMID: 20227407.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ex vivo delivery of GDNF maintains motor function and prevents neuronal loss in a transgenic mouse model of Huntington's disease. AU - Ebert,Allison D, AU - Barber,Amelia E, AU - Heins,Brittany M, AU - Svendsen,Clive N, Y1 - 2010/03/19/ PY - 2009/11/14/received PY - 2010/02/17/revised PY - 2010/03/02/accepted PY - 2010/3/16/entrez PY - 2010/3/17/pubmed PY - 2010/6/29/medline SP - 155 EP - 62 JF - Experimental neurology JO - Exp Neurol VL - 224 IS - 1 N2 - 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. SN - 1090-2430 UR - https://www.unboundmedicine.com/medline/citation/20227407/Ex_vivo_delivery_of_GDNF_maintains_motor_function_and_prevents_neuronal_loss_in_a_transgenic_mouse_model_of_Huntington's_disease_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(10)00074-9 DB - PRIME DP - Unbound Medicine ER -