Dopamine imbalance in Huntington's disease: a mechanism for the lack of behavioral flexibility
Identifieur interne : 000104 ( Main/Exploration ); précédent : 000103; suivant : 000105Dopamine imbalance in Huntington's disease: a mechanism for the lack of behavioral flexibility
Auteurs : Jane Y. Chen ; Elizabeth A. Wang ; Carlos Cepeda ; Michael S. LevineSource :
- Frontiers in Neuroscience [ 1662-4548 ] ; 2013.
Abstract
Dopamine (DA) plays an essential role in the control of coordinated movements. Alterations in DA balance in the striatum lead to pathological conditions such as Parkinson's and Huntington's diseases (HD). HD is a progressive, invariably fatal neurodegenerative disease caused by a genetic mutation producing an expansion of glutamine repeats and is characterized by abnormal dance-like movements (chorea). The principal pathology is the loss of striatal and cortical projection neurons. Changes in brain DA content and receptor number contribute to abnormal movements and cognitive deficits in HD. In particular, during the early hyperkinetic stage of HD, DA levels are increased whereas expression of DA receptors is reduced. In contrast, in the late akinetic stage, DA levels are significantly decreased and resemble those of a Parkinsonian state. Time-dependent changes in DA transmission parallel biphasic changes in glutamate synaptic transmission and may enhance alterations in glutamate receptor-mediated synaptic activity. In this review, we focus on neuronal electrophysiological mechanisms that may lead to some of the motor and cognitive symptoms of HD and how they relate to dysfunction in DA neurotransmission. Based on clinical and experimental findings, we propose that some of the behavioral alterations in HD, including reduced behavioral flexibility, may be caused by altered DA modulatory function. Thus, restoring DA balance alone or in conjunction with glutamate receptor antagonists could be a viable therapeutic approach.
Url:
DOI: 10.3389/fnins.2013.00114
PubMed: 23847463
PubMed Central: 3701870
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Dopamine imbalance in Huntington's disease: a mechanism for the lack of behavioral flexibility</title><author><name sortKey="Chen, Jane Y" sort="Chen, Jane Y" uniqKey="Chen J" first="Jane Y." last="Chen">Jane Y. Chen</name></author><author><name sortKey="Wang, Elizabeth A" sort="Wang, Elizabeth A" uniqKey="Wang E" first="Elizabeth A." last="Wang">Elizabeth A. Wang</name></author><author><name sortKey="Cepeda, Carlos" sort="Cepeda, Carlos" uniqKey="Cepeda C" first="Carlos" last="Cepeda">Carlos Cepeda</name></author><author><name sortKey="Levine, Michael S" sort="Levine, Michael S" uniqKey="Levine M" first="Michael S." last="Levine">Michael S. Levine</name></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23847463</idno><idno type="pmc">3701870</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3701870</idno><idno type="RBID">PMC:3701870</idno><idno type="doi">10.3389/fnins.2013.00114</idno><date when="2013">2013</date><idno type="wicri:Area/Pmc/Corpus">000330</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000330</idno><idno type="wicri:Area/Pmc/Curation">000218</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000218</idno><idno type="wicri:Area/Pmc/Checkpoint">000085</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000085</idno><idno type="wicri:Area/Ncbi/Merge">000137</idno><idno type="wicri:Area/Ncbi/Curation">000137</idno><idno type="wicri:Area/Ncbi/Checkpoint">000137</idno><idno type="wicri:doubleKey">1662-4548:2013:Chen J:dopamine:imbalance:in</idno><idno type="wicri:Area/Main/Merge">000104</idno><idno type="wicri:Area/Main/Curation">000104</idno><idno type="wicri:Area/Main/Exploration">000104</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Dopamine imbalance in Huntington's disease: a mechanism for the lack of behavioral flexibility</title><author><name sortKey="Chen, Jane Y" sort="Chen, Jane Y" uniqKey="Chen J" first="Jane Y." last="Chen">Jane Y. Chen</name></author><author><name sortKey="Wang, Elizabeth A" sort="Wang, Elizabeth A" uniqKey="Wang E" first="Elizabeth A." last="Wang">Elizabeth A. Wang</name></author><author><name sortKey="Cepeda, Carlos" sort="Cepeda, Carlos" uniqKey="Cepeda C" first="Carlos" last="Cepeda">Carlos Cepeda</name></author><author><name sortKey="Levine, Michael S" sort="Levine, Michael S" uniqKey="Levine M" first="Michael S." last="Levine">Michael S. Levine</name></author></analytic><series><title level="j">Frontiers in Neuroscience</title><idno type="ISSN">1662-4548</idno><idno type="eISSN">1662-453X</idno><imprint><date when="2013">2013</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Dopamine (DA) plays an essential role in the control of coordinated movements. Alterations in DA balance in the striatum lead to pathological conditions such as Parkinson's and Huntington's diseases (HD). HD is a progressive, invariably fatal neurodegenerative disease caused by a genetic mutation producing an expansion of glutamine repeats and is characterized by abnormal dance-like movements (chorea). The principal pathology is the loss of striatal and cortical projection neurons. Changes in brain DA content and receptor number contribute to abnormal movements and cognitive deficits in HD. In particular, during the early hyperkinetic stage of HD, DA levels are increased whereas expression of DA receptors is reduced. In contrast, in the late akinetic stage, DA levels are significantly decreased and resemble those of a Parkinsonian state. Time-dependent changes in DA transmission parallel biphasic changes in glutamate synaptic transmission and may enhance alterations in glutamate receptor-mediated synaptic activity. In this review, we focus on neuronal electrophysiological mechanisms that may lead to some of the motor and cognitive symptoms of HD and how they relate to dysfunction in DA neurotransmission. Based on clinical and experimental findings, we propose that some of the behavioral alterations in HD, including reduced behavioral flexibility, may be caused by altered DA modulatory function. Thus, restoring DA balance alone or in conjunction with glutamate receptor antagonists could be a viable therapeutic approach.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Afifi, A K" uniqKey="Afifi A">A. K. Afifi</name></author><author><name sortKey="Bahuth, N B" uniqKey="Bahuth N">N. B. Bahuth</name></author><author><name sortKey="Kaelber, W W" uniqKey="Kaelber W">W. W. Kaelber</name></author><author><name sortKey="Mikhael, E" uniqKey="Mikhael E">E. Mikhael</name></author><author><name sortKey="Nassar, S" uniqKey="Nassar S">S. 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Shehadeh</name></author><author><name sortKey="Wellington, C L" uniqKey="Wellington C">C. L. Wellington</name></author><author><name sortKey="Leavitt, B R" uniqKey="Leavitt B">B. R. Leavitt</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zeron, M M" uniqKey="Zeron M">M. M. Zeron</name></author><author><name sortKey="Hansson, O" uniqKey="Hansson O">O. Hansson</name></author><author><name sortKey="Chen, N" uniqKey="Chen N">N. Chen</name></author><author><name sortKey="Wellington, C L" uniqKey="Wellington C">C. L. Wellington</name></author><author><name sortKey="Leavitt, B R" uniqKey="Leavitt B">B. R. Leavitt</name></author><author><name sortKey="Brundin, P" uniqKey="Brundin P">P. Brundin</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Zhou, F M" uniqKey="Zhou F">F. M. Zhou</name></author><author><name sortKey="Wilson, C J" uniqKey="Wilson C">C. J. Wilson</name></author><author><name sortKey="Dani, J A" uniqKey="Dani J">J. A. Dani</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list></list><tree><noCountry><name sortKey="Cepeda, Carlos" sort="Cepeda, Carlos" uniqKey="Cepeda C" first="Carlos" last="Cepeda">Carlos Cepeda</name><name sortKey="Chen, Jane Y" sort="Chen, Jane Y" uniqKey="Chen J" first="Jane Y." last="Chen">Jane Y. Chen</name><name sortKey="Levine, Michael S" sort="Levine, Michael S" uniqKey="Levine M" first="Michael S." last="Levine">Michael S. Levine</name><name sortKey="Wang, Elizabeth A" sort="Wang, Elizabeth A" uniqKey="Wang E" first="Elizabeth A." last="Wang">Elizabeth A. Wang</name></noCountry></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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