Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF
This study assessed the potential for functional and anatomical recovery of the diseased aged primate nigrostriatal system, in response to trophic factor gene transfer. Aged rhesus monkeys received a single intracarotid infusion of MPTP, followed one week later by MRI-guided stereotaxic intrastriata...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2009-11-01
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| Series: | Neurobiology of Disease |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996109002010 |
| _version_ | 1830193448277245952 |
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| author | M.E. Emborg J. Moirano J. Raschke V. Bondarenko R. Zufferey S. Peng A.D. Ebert V. Joers B. Roitberg J.E. Holden J. Koprich J. Lipton J.H. Kordower P. Aebischer |
| author_facet | M.E. Emborg J. Moirano J. Raschke V. Bondarenko R. Zufferey S. Peng A.D. Ebert V. Joers B. Roitberg J.E. Holden J. Koprich J. Lipton J.H. Kordower P. Aebischer |
| author_sort | M.E. Emborg |
| collection | DOAJ |
| description | This study assessed the potential for functional and anatomical recovery of the diseased aged primate nigrostriatal system, in response to trophic factor gene transfer. Aged rhesus monkeys received a single intracarotid infusion of MPTP, followed one week later by MRI-guided stereotaxic intrastriatal and intranigral injections of lentiviral vectors encoding for glial derived neurotrophic factor (lenti-GDNF) or beta-galactosidase (lenti-LacZ). Functional analysis revealed that the lenti-GDNF, but not lenti-LacZ treated monkeys displayed behavioral improvements that were associated with increased fluorodopa uptake in the striatum ipsilateral to lenti-GDNF treatment. GDNF ELISA of striatal brain samples confirmed increased GDNF expression in lenti-GDNF treated aged animals that correlated with functional improvements and preserved nigrostriatal dopaminergic markers. Our results indicate that the aged primate brain challenged by MPTP administration has the potential to respond to trophic factor delivery and that the degree of neuroprotection depends on GDNF levels. |
| first_indexed | 2024-12-18T00:13:37Z |
| format | Article |
| id | doaj.art-de2072893d4d4dc38ef90d0bdf1ea672 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-18T00:13:37Z |
| publishDate | 2009-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-de2072893d4d4dc38ef90d0bdf1ea6722022-12-21T21:27:35ZengElsevierNeurobiology of Disease1095-953X2009-11-01362303311Response of aged parkinsonian monkeys to in vivo gene transfer of GDNFM.E. Emborg0J. Moirano1J. Raschke2V. Bondarenko3R. Zufferey4S. Peng5A.D. Ebert6V. Joers7B. Roitberg8J.E. Holden9J. Koprich10J. Lipton11J.H. Kordower12P. Aebischer13Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USA; Department of Medical Physics, University of Wisconsin, Madison, WI, USA; Corresponding author. Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USA. Fax: +1 608 263 3524.Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USA; Department of Medical Physics, University of Wisconsin, Madison, WI, USAPreclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USAPreclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USALausanne University, SwitzerlandPreclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USAWaisman Center, University of Wisconsin, Madison, WI, USAPreclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USADepartment Neurosurgery, University of Illinois, Chicago, IL, USAPreclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin - Madison, 1223 Capitol Court, Madison, WI 53715, USAToronto Western Hospital, Toronto, ON, CanadaDepartment Psychiatry, University of Cincinnati, OH, USADepartment Neurological Sciences, Rush University, Chicago, IL, USAWaisman Center, University of Wisconsin, Madison, WI, USAThis study assessed the potential for functional and anatomical recovery of the diseased aged primate nigrostriatal system, in response to trophic factor gene transfer. Aged rhesus monkeys received a single intracarotid infusion of MPTP, followed one week later by MRI-guided stereotaxic intrastriatal and intranigral injections of lentiviral vectors encoding for glial derived neurotrophic factor (lenti-GDNF) or beta-galactosidase (lenti-LacZ). Functional analysis revealed that the lenti-GDNF, but not lenti-LacZ treated monkeys displayed behavioral improvements that were associated with increased fluorodopa uptake in the striatum ipsilateral to lenti-GDNF treatment. GDNF ELISA of striatal brain samples confirmed increased GDNF expression in lenti-GDNF treated aged animals that correlated with functional improvements and preserved nigrostriatal dopaminergic markers. Our results indicate that the aged primate brain challenged by MPTP administration has the potential to respond to trophic factor delivery and that the degree of neuroprotection depends on GDNF levels.http://www.sciencedirect.com/science/article/pii/S0969996109002010MacaqueMPTPGDNFGene transferParkinson's diseaseAging |
| spellingShingle | M.E. Emborg J. Moirano J. Raschke V. Bondarenko R. Zufferey S. Peng A.D. Ebert V. Joers B. Roitberg J.E. Holden J. Koprich J. Lipton J.H. Kordower P. Aebischer Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF Neurobiology of Disease Macaque MPTP GDNF Gene transfer Parkinson's disease Aging |
| title | Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF |
| title_full | Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF |
| title_fullStr | Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF |
| title_full_unstemmed | Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF |
| title_short | Response of aged parkinsonian monkeys to in vivo gene transfer of GDNF |
| title_sort | response of aged parkinsonian monkeys to in vivo gene transfer of gdnf |
| topic | Macaque MPTP GDNF Gene transfer Parkinson's disease Aging |
| url | http://www.sciencedirect.com/science/article/pii/S0969996109002010 |
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