Source:http://linkedlifedata.com/resource/pubmed/id/15790539
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2005-3-25
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pubmed:abstractText |
Gene transfer of glial cell line-derived neurotrophic factor (GDNF) in rodent models of Parkinson's disease (PD) has been shown to protect against neurodegeneration either prior to or immediately after neurotoxin-induced lesions; however, the nigrostriatal pathway was largely intact when gene delivery was completed in these models, which may not accurately reflect the clinical situation encountered with Parkinson's patients. In this study, replication-incompetent adenoviral vectors encoding the rat GDNF gene were administered into the striatum 4 weeks following 6-hydroxydopamine (6-OHDA) injection in the unilateral striatum, more closely resembling fully developed PD. Apomorphine-induced rotational behavior testing was performed every week following 6-OHDA injection. At the 10th week after gene transfer, the striatal dopamine concentrations were measured by HPLC with an electrochemical detector and the number of tyrosine hydroxylase (TH)-positive dopamine neurons in the substantia nigra (SN) was determined by immunohistochemistry. Injection of 6-OHDA into the striatum produced stable increases in rotation, which reached a plateau between 4 and 5 weeks post-injection. The number of TH-positive neuron in the SN and dopamine levels in the striatum was significantly lower in the 6-OHDA group compared to the normal group. Gene transfer of GDNF, but not beta-galactosidase, significantly increased the number of TH-positive neurons and dopamine levels, with a subsequent behavioral recovery between 5 and 10 weeks following GDNF transduction. These findings demonstrate that adenovirus-mediated gene transfer of GDNF is efficacious even in the late stages of 6-OHDA-induced PD rats. They also provide further evidence on the effectiveness of GDNF-based gene therapy for experimental Parkinson's disease.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adrenergic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Gdnf protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Glial Cell Line-Derived...,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Oxidopamine,
http://linkedlifedata.com/resource/pubmed/chemical/Tyrosine 3-Monooxygenase
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0169-328X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
24
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pubmed:volume |
134
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
155-61
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15790539-Adenoviridae,
pubmed-meshheading:15790539-Adrenergic Agents,
pubmed-meshheading:15790539-Analysis of Variance,
pubmed-meshheading:15790539-Animals,
pubmed-meshheading:15790539-Behavior, Animal,
pubmed-meshheading:15790539-Cell Count,
pubmed-meshheading:15790539-Corpus Striatum,
pubmed-meshheading:15790539-Disease Models, Animal,
pubmed-meshheading:15790539-Dopamine,
pubmed-meshheading:15790539-Gene Expression,
pubmed-meshheading:15790539-Gene Expression Regulation,
pubmed-meshheading:15790539-Gene Therapy,
pubmed-meshheading:15790539-Genetic Vectors,
pubmed-meshheading:15790539-Glial Cell Line-Derived Neurotrophic Factor,
pubmed-meshheading:15790539-Immunohistochemistry,
pubmed-meshheading:15790539-Male,
pubmed-meshheading:15790539-Motor Activity,
pubmed-meshheading:15790539-Nerve Growth Factors,
pubmed-meshheading:15790539-Oxidopamine,
pubmed-meshheading:15790539-Parkinson Disease,
pubmed-meshheading:15790539-Rats,
pubmed-meshheading:15790539-Rats, Sprague-Dawley,
pubmed-meshheading:15790539-Rotarod Performance Test,
pubmed-meshheading:15790539-Time Factors,
pubmed-meshheading:15790539-Tyrosine 3-Monooxygenase
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pubmed:year |
2005
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pubmed:articleTitle |
Delayed gene therapy of glial cell line-derived neurotrophic factor is efficacious in a rat model of Parkinson's disease.
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pubmed:affiliation |
Department of Neurosurgery, the First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310003, China.
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pubmed:publicationType |
Journal Article,
Comparative Study
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