Aging Reduces the Neuroprotective Capacity, VEGF Secretion, and Metabolic Activity of Rat Choroid Plexus Epithelial Cells
Delivery of neurotrophic molecules to the brain has potential for preventing neuronal loss in neurodegenerative disorders. Choroid plexus (CP) epithelial cells secrete numerous neurotrophic factors, and encapsulated CP transplants are neuroprotective in models of stroke and Huntington's disease...
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2007-08-01
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Online Access: | https://doi.org/10.3727/000000007783465145 |
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doaj-ac39d00d3eae4a898bb6e9db9896755d2020-11-25T03:07:36ZengSAGE PublishingCell Transplantation0963-68971555-38922007-08-011610.3727/000000007783465145Aging Reduces the Neuroprotective Capacity, VEGF Secretion, and Metabolic Activity of Rat Choroid Plexus Epithelial CellsDwaine F. Emerich0Patricia Schneider1Briannan Bintz2Jebecka Hudak3Christopher G. Thanos4LCT BioPharma, Inc., Providence, RI, USALCT BioPharma, Inc., Providence, RI, USALCT BioPharma, Inc., Providence, RI, USALCT BioPharma, Inc., Providence, RI, USALCT BioPharma, Inc., Providence, RI, USADelivery of neurotrophic molecules to the brain has potential for preventing neuronal loss in neurodegenerative disorders. Choroid plexus (CP) epithelial cells secrete numerous neurotrophic factors, and encapsulated CP transplants are neuroprotective in models of stroke and Huntington's disease (HD). To date, all studies examining the neuroprotective potential of CP transplants have used cells isolated from young donor animals. Because the aging process significantly impacts the cytoarchitecture and function of the CP the following studies determined whether age-related impairments occur in its neuroprotective capacity. CP was isolated from either young (3–4 months) or aged (24 months) rats. In vitro, young CP epithelial cells secreted more VEGF and were metabolically more active than aged CP epithelial cells. Additionally, conditioned medium from cultured aged CP was less potent than young CP at enhancing the survival of serum-deprived neurons. Finally, encapsulated CP was tested in an animal model of HD. Cell-loaded or empty alginate capsules (control group) were transplanted unilaterally into the rat striatum. Seven days later, the animals received an injection of quinolinic acid (QA; 225 nmol) adjacent to the implant site. Animals were tested for motor function 28 days later. In the control group, QA lesions severely impaired function of the contralateral forelimb. Implants of young CP were potently neuroprotective as rats receiving CP transplants were not significantly impaired when tested for motor function. In contrast, implants of CP from aged rats were only modestly effective and were much less potent than young CP transplants. These data are the first to directly link aging with diminished neuroprotective capacity of CP epithelial cells.https://doi.org/10.3727/000000007783465145 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Dwaine F. Emerich Patricia Schneider Briannan Bintz Jebecka Hudak Christopher G. Thanos |
spellingShingle |
Dwaine F. Emerich Patricia Schneider Briannan Bintz Jebecka Hudak Christopher G. Thanos Aging Reduces the Neuroprotective Capacity, VEGF Secretion, and Metabolic Activity of Rat Choroid Plexus Epithelial Cells Cell Transplantation |
author_facet |
Dwaine F. Emerich Patricia Schneider Briannan Bintz Jebecka Hudak Christopher G. Thanos |
author_sort |
Dwaine F. Emerich |
title |
Aging Reduces the Neuroprotective Capacity, VEGF Secretion, and Metabolic Activity of Rat Choroid Plexus Epithelial Cells |
title_short |
Aging Reduces the Neuroprotective Capacity, VEGF Secretion, and Metabolic Activity of Rat Choroid Plexus Epithelial Cells |
title_full |
Aging Reduces the Neuroprotective Capacity, VEGF Secretion, and Metabolic Activity of Rat Choroid Plexus Epithelial Cells |
title_fullStr |
Aging Reduces the Neuroprotective Capacity, VEGF Secretion, and Metabolic Activity of Rat Choroid Plexus Epithelial Cells |
title_full_unstemmed |
Aging Reduces the Neuroprotective Capacity, VEGF Secretion, and Metabolic Activity of Rat Choroid Plexus Epithelial Cells |
title_sort |
aging reduces the neuroprotective capacity, vegf secretion, and metabolic activity of rat choroid plexus epithelial cells |
publisher |
SAGE Publishing |
series |
Cell Transplantation |
issn |
0963-6897 1555-3892 |
publishDate |
2007-08-01 |
description |
Delivery of neurotrophic molecules to the brain has potential for preventing neuronal loss in neurodegenerative disorders. Choroid plexus (CP) epithelial cells secrete numerous neurotrophic factors, and encapsulated CP transplants are neuroprotective in models of stroke and Huntington's disease (HD). To date, all studies examining the neuroprotective potential of CP transplants have used cells isolated from young donor animals. Because the aging process significantly impacts the cytoarchitecture and function of the CP the following studies determined whether age-related impairments occur in its neuroprotective capacity. CP was isolated from either young (3–4 months) or aged (24 months) rats. In vitro, young CP epithelial cells secreted more VEGF and were metabolically more active than aged CP epithelial cells. Additionally, conditioned medium from cultured aged CP was less potent than young CP at enhancing the survival of serum-deprived neurons. Finally, encapsulated CP was tested in an animal model of HD. Cell-loaded or empty alginate capsules (control group) were transplanted unilaterally into the rat striatum. Seven days later, the animals received an injection of quinolinic acid (QA; 225 nmol) adjacent to the implant site. Animals were tested for motor function 28 days later. In the control group, QA lesions severely impaired function of the contralateral forelimb. Implants of young CP were potently neuroprotective as rats receiving CP transplants were not significantly impaired when tested for motor function. In contrast, implants of CP from aged rats were only modestly effective and were much less potent than young CP transplants. These data are the first to directly link aging with diminished neuroprotective capacity of CP epithelial cells. |
url |
https://doi.org/10.3727/000000007783465145 |
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