Interrogating the aged striatum: Robust survival of grafted dopamine neurons in aging rats produces inferior behavioral recovery and evidence of impaired integration
Advanced age is the primary risk factor for Parkinson's disease (PD). In PD patients and rodent models of PD, advanced age is associated with inferior symptomatic benefit following intrastriatal grafting of embryonic dopamine (DA) neurons, a pattern believed to result from decreased survival an...
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Elsevier
2015-05-01
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Series: | Neurobiology of Disease |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996115000674 |
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doaj-237621f88f434677a865b0966fea3365 |
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Article |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Timothy J. Collier Jennifer O'Malley David J. Rademacher Jennifer A. Stancati Kellie A. Sisson Caryl E. Sortwell Katrina L. Paumier Kibrom G. Gebremedhin Kathy Steece-Collier |
spellingShingle |
Timothy J. Collier Jennifer O'Malley David J. Rademacher Jennifer A. Stancati Kellie A. Sisson Caryl E. Sortwell Katrina L. Paumier Kibrom G. Gebremedhin Kathy Steece-Collier Interrogating the aged striatum: Robust survival of grafted dopamine neurons in aging rats produces inferior behavioral recovery and evidence of impaired integration Neurobiology of Disease Parkinson's disease Aging Rodent Grafting Dyskinesias Levodopa |
author_facet |
Timothy J. Collier Jennifer O'Malley David J. Rademacher Jennifer A. Stancati Kellie A. Sisson Caryl E. Sortwell Katrina L. Paumier Kibrom G. Gebremedhin Kathy Steece-Collier |
author_sort |
Timothy J. Collier |
title |
Interrogating the aged striatum: Robust survival of grafted dopamine neurons in aging rats produces inferior behavioral recovery and evidence of impaired integration |
title_short |
Interrogating the aged striatum: Robust survival of grafted dopamine neurons in aging rats produces inferior behavioral recovery and evidence of impaired integration |
title_full |
Interrogating the aged striatum: Robust survival of grafted dopamine neurons in aging rats produces inferior behavioral recovery and evidence of impaired integration |
title_fullStr |
Interrogating the aged striatum: Robust survival of grafted dopamine neurons in aging rats produces inferior behavioral recovery and evidence of impaired integration |
title_full_unstemmed |
Interrogating the aged striatum: Robust survival of grafted dopamine neurons in aging rats produces inferior behavioral recovery and evidence of impaired integration |
title_sort |
interrogating the aged striatum: robust survival of grafted dopamine neurons in aging rats produces inferior behavioral recovery and evidence of impaired integration |
publisher |
Elsevier |
series |
Neurobiology of Disease |
issn |
1095-953X |
publishDate |
2015-05-01 |
description |
Advanced age is the primary risk factor for Parkinson's disease (PD). In PD patients and rodent models of PD, advanced age is associated with inferior symptomatic benefit following intrastriatal grafting of embryonic dopamine (DA) neurons, a pattern believed to result from decreased survival and reinnervation provided by grafted neurons in the aged host. To help understand the capacity of the aged, parkinsonian striatum to be remodeled with new DA terminals, we used a grafting model and examined whether increasing the number of grafted DA neurons in aged rats would translate to enhanced behavioral recovery. Young (3 months), middle-aged (15 months), and aged (22 months) parkinsonian rats were grafted with proportionately increasing numbers of embryonic ventral mesencephalic (VM) cells to evaluate whether the limitations of the graft environment in subjects of advancing age can be offset by increased numbers of transplanted neurons. Despite robust survival of grafted neurons in aged rats, reinnervation of striatal neurons remained inferior and amelioration of levodopa-induced dyskinesias (LID) was delayed or absent. This study demonstrates that: 1) counter to previous evidence, under certain conditions the aged striatum can support robust survival of grafted DA neurons; and 2) unknown factors associated with the aged striatum result in inferior integration of graft and host, and continue to present obstacles to full therapeutic efficacy of DA cell-based therapy in this model of aging. |
topic |
Parkinson's disease Aging Rodent Grafting Dyskinesias Levodopa |
url |
http://www.sciencedirect.com/science/article/pii/S0969996115000674 |
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doaj-237621f88f434677a865b0966fea33652021-03-22T12:42:42ZengElsevierNeurobiology of Disease1095-953X2015-05-0177191203Interrogating the aged striatum: Robust survival of grafted dopamine neurons in aging rats produces inferior behavioral recovery and evidence of impaired integrationTimothy J. Collier0Jennifer O'Malley1David J. Rademacher2Jennifer A. Stancati3Kellie A. Sisson4Caryl E. Sortwell5Katrina L. Paumier6Kibrom G. Gebremedhin7Kathy Steece-Collier8Michigan State University, College of Human Medicine, Department of Translational Science and Molecular Medicine & The Udall Center of Excellence in Parkinson's Disease Research, 333 Bostwick Ave NE, Grand Rapids, MI 49503, USACincinnati Children's Hospital Medical Center, Division of Child Neurology, 3333 Burnet Avenue, Cincinnati, OH 45229, USALake Forest College, Department of Psychology, 555 N Sheridan Rd, Lake Forest, IL 60045, USAMichigan State University, College of Human Medicine, Department of Translational Science and Molecular Medicine & The Udall Center of Excellence in Parkinson's Disease Research, 333 Bostwick Ave NE, Grand Rapids, MI 49503, USAMichigan State University, College of Human Medicine, Department of Translational Science and Molecular Medicine & The Udall Center of Excellence in Parkinson's Disease Research, 333 Bostwick Ave NE, Grand Rapids, MI 49503, USAMichigan State University, College of Human Medicine, Department of Translational Science and Molecular Medicine & The Udall Center of Excellence in Parkinson's Disease Research, 333 Bostwick Ave NE, Grand Rapids, MI 49503, USAMichigan State University, College of Human Medicine, Department of Translational Science and Molecular Medicine & The Udall Center of Excellence in Parkinson's Disease Research, 333 Bostwick Ave NE, Grand Rapids, MI 49503, USAMichigan State University, College of Human Medicine, Department of Translational Science and Molecular Medicine & The Udall Center of Excellence in Parkinson's Disease Research, 333 Bostwick Ave NE, Grand Rapids, MI 49503, USAMichigan State University, College of Human Medicine, Department of Translational Science and Molecular Medicine & The Udall Center of Excellence in Parkinson's Disease Research, 333 Bostwick Ave NE, Grand Rapids, MI 49503, USA; Corresponding author at: Department of Translational Science & Molecular Medicine, Michigan State University, 333 Bostwick Avenue NE, Grand Rapids, MI 49503, USA. Fax: +1 616 234 0990.Advanced age is the primary risk factor for Parkinson's disease (PD). In PD patients and rodent models of PD, advanced age is associated with inferior symptomatic benefit following intrastriatal grafting of embryonic dopamine (DA) neurons, a pattern believed to result from decreased survival and reinnervation provided by grafted neurons in the aged host. To help understand the capacity of the aged, parkinsonian striatum to be remodeled with new DA terminals, we used a grafting model and examined whether increasing the number of grafted DA neurons in aged rats would translate to enhanced behavioral recovery. Young (3 months), middle-aged (15 months), and aged (22 months) parkinsonian rats were grafted with proportionately increasing numbers of embryonic ventral mesencephalic (VM) cells to evaluate whether the limitations of the graft environment in subjects of advancing age can be offset by increased numbers of transplanted neurons. Despite robust survival of grafted neurons in aged rats, reinnervation of striatal neurons remained inferior and amelioration of levodopa-induced dyskinesias (LID) was delayed or absent. This study demonstrates that: 1) counter to previous evidence, under certain conditions the aged striatum can support robust survival of grafted DA neurons; and 2) unknown factors associated with the aged striatum result in inferior integration of graft and host, and continue to present obstacles to full therapeutic efficacy of DA cell-based therapy in this model of aging.http://www.sciencedirect.com/science/article/pii/S0969996115000674Parkinson's diseaseAgingRodentGraftingDyskinesiasLevodopa |