Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2005-3-25
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0169-328X
pubmed:author
pubmed:issnType
Print
pubmed:day
24
pubmed:volume
134
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
155-61
pubmed:dateRevised
2006-11-15
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
pubmed:year
2005
pubmed:articleTitle
Delayed gene therapy of glial cell line-derived neurotrophic factor is efficacious in a rat model of Parkinson's disease.
pubmed:affiliation
Department of Neurosurgery, the First Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310003, China.
pubmed:publicationType
Journal Article, Comparative Study