Linked Life Data

10023444

Source:http://linkedlifedata.com/resource/pubmed/id/10023444

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1999-3-9
pubmed:abstractText
Parkinson's disease is a neurodegenerative disorder characterized by the depletion of dopamine in the caudate putamen. Dopamine replacement with levodopa, a precursor of the neurotransmitter, is presently the most common treatment for this disease. However, in an effort to obtain better therapeutic results, tissue or cells that synthesize catecholamines have been grafted into experimental animals and human patients. In this paper, we present a novel technique to express tyrosine hydroxylase (TH) in the host's own astrocytes. This procedure uses a transgene in which the expression of a TH cDNA is under the control of a glial fibrillary acidic protein (GFAP) promoter, which confers astrocyte-specific expression and also increases its activity in response to brain injury. The method was tested in a rat model of Parkinson's disease produced by lesioning the striatum with 6-hydroxydopamine. Following microinjection of the transgene into the denervated striatum as a DNA-liposome complex, expression of the transgene was detected by RT-PCR and TH protein was observed specifically in astrocytes by using double-labeling immunofluorescence for GFAP and TH coupled with laser confocal microscopy. Efficacy was demonstrated by significant behavioral recovery, as assessed by a decrease in the pharmacologically induced turning behavior generated by the unilateral denervation of the rat striatum. These results suggest this is a valuable technique to express molecules of therapeutic interest in the brain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
5
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1650-5
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:10023444-Animals, pubmed-meshheading:10023444-Astrocytes, pubmed-meshheading:10023444-Gene Expression, pubmed-meshheading:10023444-Gene Therapy, pubmed-meshheading:10023444-Gene Transfer Techniques, pubmed-meshheading:10023444-Glial Fibrillary Acidic Protein, pubmed-meshheading:10023444-Liposomes, pubmed-meshheading:10023444-Microinjections, pubmed-meshheading:10023444-Microscopy, Confocal, pubmed-meshheading:10023444-Microscopy, Fluorescence, pubmed-meshheading:10023444-Oxidopamine, pubmed-meshheading:10023444-Parkinson Disease, Secondary, pubmed-meshheading:10023444-Phosphatidylethanolamines, pubmed-meshheading:10023444-Promoter Regions, Genetic, pubmed-meshheading:10023444-RNA, Messenger, pubmed-meshheading:10023444-Rats, pubmed-meshheading:10023444-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:10023444-Tyrosine 3-Monooxygenase, pubmed-meshheading:10023444-beta-Galactosidase
pubmed:year
1998
pubmed:articleTitle
Astrocyte-specific expression of tyrosine hydroxylase after intracerebral gene transfer induces behavioral recovery in experimental parkinsonism.
pubmed:affiliation
Departamento de Fisiología, Biofísica y Neurociencias, Centro de Investigación y de Estudios Avanzados del IPN, México, México, D.F.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't