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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1-2
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pubmed:dateCreated |
1999-3-12
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pubmed:abstractText |
Microdialysis measurements of dopamine (DA) and DA metabolites were carried out in the putamen and substantia nigra of unilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-lesioned rhesus monkeys that received intraventricular injections of vehicle or glial-derived neurotrophic factor (GDNF, 300 microg) 3 weeks prior to the microdialysis studies. Following behavioral measures in the MPTP-lesioned monkeys, they were anesthetized with isoflurane and placed in a stereotaxic apparatus. Magnetic resonance imaging (MRI)-guided sterile stereotaxic procedures were used for implantations of the microdialysis probes. Basal extracellular levels of DA and the DA metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were found to be decreased by >95% in the right putamen of the MPTP-lesioned monkeys as compared to normal animals. In contrast, basal DA levels were not significantly decreased, and DOPAC and HVA levels were decreased by only 65% and 30%, respectively, in the MPTP-lesioned substantia nigra. Significant reductions in d-amphetamine-evoked DA release were also observed in the MPTP-lesioned substantia nigra and putamen of the monkeys as compared to normal animals. A single intraventricular administration of GDNF into one group of MPTP-lesioned monkeys elicited improvements in the parkinsonian symptoms in these animals at 2-3 weeks post-administration. In addition, d-amphetamine-evoked overflow of DA was significantly increased in the substantia nigra but not the putamen of MPTP-lesioned monkeys that had received GDNF. Moreover, post-mortem brain tissue studies showed increases in whole tissue levels of DA and DA metabolite levels primarily within the substantia nigra in MPTP-lesioned monkeys that had received GDNF. Taken together, these data support that single ventricular infusions of GDNF produce improvements in motoric behavior in MPTP-lesioned monkeys that correlate with increases in DA neuronal function that are localized to the substantia nigra and not the putamen.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3,4-Dihydroxyphenylacetic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Dextroamphetamine,
http://linkedlifedata.com/resource/pubmed/chemical/Dopamine Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Glial Cell Line-Derived...,
http://linkedlifedata.com/resource/pubmed/chemical/Homovanillic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0006-8993
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pubmed:author | |
pubmed:copyrightInfo |
Copyright 1999 Elsevier Science B.V.
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pubmed:issnType |
Print
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pubmed:day |
30
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pubmed:volume |
817
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
163-71
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9889359-3,4-Dihydroxyphenylacetic Acid,
pubmed-meshheading:9889359-Animals,
pubmed-meshheading:9889359-Basal Metabolism,
pubmed-meshheading:9889359-Dextroamphetamine,
pubmed-meshheading:9889359-Dopamine,
pubmed-meshheading:9889359-Dopamine Agents,
pubmed-meshheading:9889359-Female,
pubmed-meshheading:9889359-Functional Laterality,
pubmed-meshheading:9889359-Glial Cell Line-Derived Neurotrophic Factor,
pubmed-meshheading:9889359-Homovanillic Acid,
pubmed-meshheading:9889359-MPTP Poisoning,
pubmed-meshheading:9889359-Macaca mulatta,
pubmed-meshheading:9889359-Microdialysis,
pubmed-meshheading:9889359-Nerve Growth Factors,
pubmed-meshheading:9889359-Nerve Tissue Proteins,
pubmed-meshheading:9889359-Putamen,
pubmed-meshheading:9889359-Substantia Nigra
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pubmed:year |
1999
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pubmed:articleTitle |
GDNF improves dopamine function in the substantia nigra but not the putamen of unilateral MPTP-lesioned rhesus monkeys.
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pubmed:affiliation |
Departments of Psychiatry and Pharmacology, University of Colorado Health Sciences Center, 4200 E. Ninth Avenue, Campus Box C268-71, Denver, CO, USA. greg.gerhardt@uchsc.edu
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.
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