Behavioural effects of genetically engineered cells releasing dopa and dopamine after intracerebral grafting in a rat model of Parkinson's disease.
Identifieur interne : 001768 ( PubMed/Curation ); précédent : 001767; suivant : 001769Behavioural effects of genetically engineered cells releasing dopa and dopamine after intracerebral grafting in a rat model of Parkinson's disease.
Auteurs : P. Horellou [France] ; C. Lundberg ; B. Le Bourdellès ; K. Wictorin ; P. Brundin ; P. Kalén ; A. Björklund ; J. MalletSource :
- Journal de physiologie [ 0021-7948 ] ; 1991.
English descriptors
- KwdEn :
- Animals, Catechols (metabolism), Corpus Striatum (metabolism), Corpus Striatum (transplantation), Dihydroxyphenylalanine (pharmacokinetics), Dihydroxyphenylalanine (pharmacology), Disease Models, Animal, Dopamine (pharmacokinetics), Dopamine (pharmacology), Genetic Engineering, Motor Activity (drug effects), Parkinson Disease (genetics), Parkinson Disease (metabolism), Parkinson Disease (surgery), Rats, Tyrosine 3-Monooxygenase (metabolism).
- MESH :
- chemical , metabolism : Catechols, Tyrosine 3-Monooxygenase.
- drug effects : Motor Activity.
- genetics : Parkinson Disease.
- metabolism : Corpus Striatum, Parkinson Disease.
- chemical , pharmacokinetics : Dihydroxyphenylalanine, Dopamine.
- chemical , pharmacology : Dihydroxyphenylalanine, Dopamine.
- surgery : Parkinson Disease.
- transplantation : Corpus Striatum.
- Animals, Disease Models, Animal, Genetic Engineering, Rats.
Abstract
The relative importance of synaptic versus paracrine dopamine transmission for the occurrence of functional effects following intrastriatal grafting is not fully established. In the present study we grafted cell lines, expressing the form I of human tyrosine hydroxylase after infection with a recombinant retrovirus and selection in tyrosine-free-medium, to the denervated striatum in order to analyse the extent to which extracellular dopamine levels can be restored and the effect of a diffuse release of dopamine on motor impairement in a rat model of Parkinson's disease. In petri dish, the modified fibroblast cells (NIH.3T3) release DOPA constitutively whereas the modified endocrine cells (RIN) store and release dopamine in a regulated way. Interestingly, in denervated striatum, grafts of modified fibroblast cells produce DOPA which was efficiently converted into dopamine by the host striatal tissue. In the grafted striatum, both fibroblast and endocrine cells restore subnormal levels of diffuse release of dopamine which is notably unaffected and stimulated, respectively, by high concentration of potassium, in connection with the in vitro properties of the grafted cells. The intrastriatal grafts of modified cells partially reversed the apomorphine-induced but not the amphetamine-induced motor asymmetry. We discuss the implications of these results in the context of Parkinson disease.
PubMed: 1687823
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Wictorin</name></author><author><name sortKey="Brundin, P" sort="Brundin, P" uniqKey="Brundin P" first="P" last="Brundin">P. Brundin</name></author><author><name sortKey="Kalen, P" sort="Kalen, P" uniqKey="Kalen P" first="P" last="Kalén">P. Kalén</name></author><author><name sortKey="Bjorklund, A" sort="Bjorklund, A" uniqKey="Bjorklund A" first="A" last="Björklund">A. Björklund</name></author><author><name sortKey="Mallet, J" sort="Mallet, J" uniqKey="Mallet J" first="J" last="Mallet">J. Mallet</name></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="1991">1991</date><idno type="RBID">pubmed:1687823</idno><idno type="pmid">1687823</idno><idno type="wicri:Area/PubMed/Corpus">001809</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">001809</idno><idno type="wicri:Area/PubMed/Curation">001768</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">001768</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">Behavioural effects of genetically engineered cells releasing dopa and dopamine after intracerebral grafting in a rat model of Parkinson's disease.</title><author><name sortKey="Horellou, P" sort="Horellou, P" uniqKey="Horellou P" first="P" last="Horellou">P. 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Björklund</name></author><author><name sortKey="Mallet, J" sort="Mallet, J" uniqKey="Mallet J" first="J" last="Mallet">J. Mallet</name></author></analytic><series><title level="j">Journal de physiologie</title><idno type="ISSN">0021-7948</idno><imprint><date when="1991" type="published">1991</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Catechols (metabolism)</term><term>Corpus Striatum (metabolism)</term><term>Corpus Striatum (transplantation)</term><term>Dihydroxyphenylalanine (pharmacokinetics)</term><term>Dihydroxyphenylalanine (pharmacology)</term><term>Disease Models, Animal</term><term>Dopamine (pharmacokinetics)</term><term>Dopamine (pharmacology)</term><term>Genetic Engineering</term><term>Motor Activity (drug effects)</term><term>Parkinson Disease (genetics)</term><term>Parkinson Disease (metabolism)</term><term>Parkinson Disease (surgery)</term><term>Rats</term><term>Tyrosine 3-Monooxygenase (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Catechols</term><term>Tyrosine 3-Monooxygenase</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Motor Activity</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Corpus Striatum</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Dihydroxyphenylalanine</term><term>Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Dihydroxyphenylalanine</term><term>Dopamine</term></keywords><keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="transplantation" xml:lang="en"><term>Corpus Striatum</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Genetic Engineering</term><term>Rats</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The relative importance of synaptic versus paracrine dopamine transmission for the occurrence of functional effects following intrastriatal grafting is not fully established. In the present study we grafted cell lines, expressing the form I of human tyrosine hydroxylase after infection with a recombinant retrovirus and selection in tyrosine-free-medium, to the denervated striatum in order to analyse the extent to which extracellular dopamine levels can be restored and the effect of a diffuse release of dopamine on motor impairement in a rat model of Parkinson's disease. In petri dish, the modified fibroblast cells (NIH.3T3) release DOPA constitutively whereas the modified endocrine cells (RIN) store and release dopamine in a regulated way. Interestingly, in denervated striatum, grafts of modified fibroblast cells produce DOPA which was efficiently converted into dopamine by the host striatal tissue. In the grafted striatum, both fibroblast and endocrine cells restore subnormal levels of diffuse release of dopamine which is notably unaffected and stimulated, respectively, by high concentration of potassium, in connection with the in vitro properties of the grafted cells. The intrastriatal grafts of modified cells partially reversed the apomorphine-induced but not the amphetamine-induced motor asymmetry. We discuss the implications of these results in the context of Parkinson disease.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">1687823</PMID><DateCreated><Year>1992</Year><Month>07</Month><Day>15</Day></DateCreated><DateCompleted><Year>1992</Year><Month>07</Month><Day>15</Day></DateCompleted><DateRevised><Year>2013</Year><Month>11</Month><Day>21</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Print">0021-7948</ISSN><JournalIssue CitedMedium="Print"><Volume>85</Volume><Issue>3</Issue><PubDate><Year>1991</Year></PubDate></JournalIssue><Title>Journal de physiologie</Title><ISOAbbreviation>J. Physiol. (Paris)</ISOAbbreviation></Journal><ArticleTitle>Behavioural effects of genetically engineered cells releasing dopa and dopamine after intracerebral grafting in a rat model of Parkinson's disease.</ArticleTitle><Pagination><MedlinePgn>158-70</MedlinePgn></Pagination><Abstract><AbstractText>The relative importance of synaptic versus paracrine dopamine transmission for the occurrence of functional effects following intrastriatal grafting is not fully established. In the present study we grafted cell lines, expressing the form I of human tyrosine hydroxylase after infection with a recombinant retrovirus and selection in tyrosine-free-medium, to the denervated striatum in order to analyse the extent to which extracellular dopamine levels can be restored and the effect of a diffuse release of dopamine on motor impairement in a rat model of Parkinson's disease. In petri dish, the modified fibroblast cells (NIH.3T3) release DOPA constitutively whereas the modified endocrine cells (RIN) store and release dopamine in a regulated way. Interestingly, in denervated striatum, grafts of modified fibroblast cells produce DOPA which was efficiently converted into dopamine by the host striatal tissue. In the grafted striatum, both fibroblast and endocrine cells restore subnormal levels of diffuse release of dopamine which is notably unaffected and stimulated, respectively, by high concentration of potassium, in connection with the in vitro properties of the grafted cells. The intrastriatal grafts of modified cells partially reversed the apomorphine-induced but not the amphetamine-induced motor asymmetry. 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