Striatal Molecular Signature of Subchronic Subthalamic Nucleus High Frequency Stimulation in Parkinsonian Rat
Identifieur interne : 000814 ( Pmc/Curation ); précédent : 000813; suivant : 000815Striatal Molecular Signature of Subchronic Subthalamic Nucleus High Frequency Stimulation in Parkinsonian Rat
Auteurs : Sylviane Lortet [France] ; Emilie Lacombe [France] ; Nicolas Boulanger [France] ; Pascal Rihet [France] ; Catherine Nguyen [France] ; Lydia Kerkerian-Le Goff [France] ; Pascal Salin [France]Source :
- PLoS ONE [ 1932-6203 ] ; 2013.
Abstract
This study addresses the molecular mechanisms underlying the action of subthalamic nucleus high frequency stimulation (STN-HFS) in the treatment of Parkinson's disease and its interaction with levodopa (L-DOPA), focusing on the striatum. Striatal gene expression profile was assessed in rats with nigral dopamine neuron lesion, either treated or not, using agilent microarrays and qPCR verification. The treatments consisted in anti-akinetic STN-HFS (5 days), chronic L-DOPA treatment inducing dyskinesia (LIDs) or the combination of the two treatments that exacerbated LIDs. STN-HFS modulated 71 striatal genes. The main biological processes associated with the differentially expressed gene products include regulation of growth, of apoptosis and of synaptic transmission, and extracellular region is a major cellular component implicated. In particular, several of these genes have been shown to support survival or differentiation of striatal or of dopaminergic neurons. These results indicate that STN HFS may induce widespread anatomo-functional rearrangements in the striatum and create a molecular environment favorable for neuroprotection and neuroplasticity. STN-HFS and L-DOPA treatment share very few common gene regulation features indicating that the molecular substrates underlying their striatal action are mostly different; among the common effects is the down-regulation of
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DOI: 10.1371/journal.pone.0060447
PubMed: 23593219
PubMed Central: 3617149
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Subchronic Subthalamic Nucleus High Frequency Stimulation in Parkinsonian Rat</title><author><name sortKey="Lortet, Sylviane" sort="Lortet, Sylviane" uniqKey="Lortet S" first="Sylviane" last="Lortet">Sylviane Lortet</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Aix-Marseille Université, CNRS, IBDM UMR 7288, Marseille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, CNRS, IBDM UMR 7288, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Lacombe, Emilie" sort="Lacombe, Emilie" uniqKey="Lacombe E" first="Emilie" last="Lacombe">Emilie Lacombe</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Aix-Marseille Université, CNRS, IBDM UMR 7288, Marseille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, CNRS, IBDM UMR 7288, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Boulanger, Nicolas" sort="Boulanger, Nicolas" uniqKey="Boulanger N" first="Nicolas" last="Boulanger">Nicolas Boulanger</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Aix-Marseille Université, INSERM, TAGC U1090, Marseille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, INSERM, TAGC U1090, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Rihet, Pascal" sort="Rihet, Pascal" uniqKey="Rihet P" first="Pascal" last="Rihet">Pascal Rihet</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Aix-Marseille Université, INSERM, TAGC U1090, Marseille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, INSERM, TAGC U1090, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Nguyen, Catherine" sort="Nguyen, Catherine" uniqKey="Nguyen C" first="Catherine" last="Nguyen">Catherine Nguyen</name><affiliation wicri:level="1"><nlm:aff id="aff2"><addr-line>Aix-Marseille Université, INSERM, TAGC U1090, Marseille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, INSERM, TAGC U1090, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Goff, Lydia Kerkerian Le" sort="Goff, Lydia Kerkerian Le" uniqKey="Goff L" first="Lydia Kerkerian-Le" last="Goff">Lydia Kerkerian-Le Goff</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Aix-Marseille Université, CNRS, IBDM UMR 7288, Marseille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, CNRS, IBDM UMR 7288, Marseille</wicri:regionArea></affiliation></author><author><name sortKey="Salin, Pascal" sort="Salin, Pascal" uniqKey="Salin P" first="Pascal" last="Salin">Pascal Salin</name><affiliation wicri:level="1"><nlm:aff id="aff1"><addr-line>Aix-Marseille Université, CNRS, IBDM UMR 7288, Marseille, France</addr-line></nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>Aix-Marseille Université, CNRS, IBDM UMR 7288, Marseille</wicri:regionArea></affiliation></author></analytic><series><title level="j">PLoS ONE</title><idno type="eISSN">1932-6203</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>This study addresses the molecular mechanisms underlying the action of subthalamic nucleus high frequency stimulation (STN-HFS) in the treatment of Parkinson's disease and its interaction with levodopa (L-DOPA), focusing on the striatum. Striatal gene expression profile was assessed in rats with nigral dopamine neuron lesion, either treated or not, using agilent microarrays and qPCR verification. The treatments consisted in anti-akinetic STN-HFS (5 days), chronic L-DOPA treatment inducing dyskinesia (LIDs) or the combination of the two treatments that exacerbated LIDs. STN-HFS modulated 71 striatal genes. The main biological processes associated with the differentially expressed gene products include regulation of growth, of apoptosis and of synaptic transmission, and extracellular region is a major cellular component implicated. In particular, several of these genes have been shown to support survival or differentiation of striatal or of dopaminergic neurons. These results indicate that STN HFS may induce widespread anatomo-functional rearrangements in the striatum and create a molecular environment favorable for neuroprotection and neuroplasticity. STN-HFS and L-DOPA treatment share very few common gene regulation features indicating that the molecular substrates underlying their striatal action are mostly different; among the common effects is the down-regulation of <italic>Adrb1</italic>, which encodes the adrenergic beta-1- receptor, supporting a major role of this receptor in Parkinson's disease. In addition to genes already reported to be associated with LIDs (preprodynorphin, thyrotropin-releasing hormone, metabotropic glutamate receptor 4, cannabinoid receptor 1), the comparison between DOPA and DOPA/HFS identifies immunity-related genes as potential players in L-DOPA side effects.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Dauer, W" uniqKey="Dauer W">W Dauer</name></author><author><name sortKey="Przedborski, S" uniqKey="Przedborski S">S Przedborski</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Delong, M" uniqKey="Delong M">M DeLong</name></author><author><name sortKey="Wichmann, T" uniqKey="Wichmann T">T Wichmann</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Bezard, E" uniqKey="Bezard E">E Bezard</name></author><author><name sortKey="Brotchie, Jm" uniqKey="Brotchie J">JM Brotchie</name></author><author><name sortKey="Gross, Ce" 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sortKey="Bateup, Hs" uniqKey="Bateup H">HS Bateup</name></author></analytic></biblStruct></listBibl></div1></back></TEI><pmc article-type="research-article"><pmc-dir>properties open_access</pmc-dir>
<front><journal-meta><journal-id journal-id-type="nlm-ta">PLoS One</journal-id><journal-id journal-id-type="iso-abbrev">PLoS ONE</journal-id><journal-id journal-id-type="publisher-id">plos</journal-id><journal-id journal-id-type="pmc">plosone</journal-id><journal-title-group><journal-title>PLoS ONE</journal-title></journal-title-group><issn pub-type="epub">1932-6203</issn><publisher><publisher-name>Public Library of Science</publisher-name><publisher-loc>San Francisco, USA</publisher-loc></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23593219</article-id><article-id pub-id-type="pmc">3617149</article-id><article-id pub-id-type="publisher-id">PONE-D-12-36103</article-id><article-id pub-id-type="doi">10.1371/journal.pone.0060447</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Biology</subject><subj-group><subject>Model Organisms</subject><subj-group><subject>Animal Models</subject><subj-group><subject>Rat</subject></subj-group></subj-group></subj-group><subj-group><subject>Molecular Cell Biology</subject><subj-group><subject>Gene Expression</subject><subj-group><subject>DNA transcription</subject></subj-group></subj-group><subj-group><subject>Nucleic Acids</subject><subj-group><subject>RNA</subject></subj-group></subj-group></subj-group><subj-group><subject>Neuroscience</subject><subj-group><subject>Molecular Neuroscience</subject><subject>Neurobiology of Disease and Regeneration</subject><subject>Neurotransmitters</subject></subj-group></subj-group></subj-group><subj-group subj-group-type="Discipline-v2"><subject>Medicine</subject><subj-group><subject>Neurology</subject><subj-group><subject>Movement Disorders</subject><subject>Parkinson Disease</subject></subj-group></subj-group></subj-group></article-categories><title-group><article-title>Striatal Molecular Signature of Subchronic Subthalamic Nucleus High Frequency Stimulation in Parkinsonian Rat</article-title><alt-title alt-title-type="running-head">Striatal Gene Profiling after STN-HFS</alt-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>Lortet</surname><given-names>Sylviane</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="corresp" rid="cor1"><sup>*</sup></xref></contrib><contrib contrib-type="author"><name><surname>Lacombe</surname><given-names>Emilie</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Boulanger</surname><given-names>Nicolas</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Rihet</surname><given-names>Pascal</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Nguyen</surname><given-names>Catherine</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref></contrib><contrib contrib-type="author"><name><surname>Goff</surname><given-names>Lydia Kerkerian-Le</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib><contrib contrib-type="author"><name><surname>Salin</surname><given-names>Pascal</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref></contrib></contrib-group><aff id="aff1"><label>1</label><addr-line>Aix-Marseille Université, CNRS, IBDM UMR 7288, Marseille, France</addr-line></aff><aff id="aff2"><label>2</label><addr-line>Aix-Marseille Université, INSERM, TAGC U1090, Marseille, France</addr-line></aff><contrib-group><contrib contrib-type="editor"><name><surname>Svenningsson</surname><given-names>Per</given-names></name><role>Editor</role><xref ref-type="aff" rid="edit1"></xref></contrib></contrib-group><aff id="edit1"><addr-line>Karolinska Institute, Sweden</addr-line></aff><author-notes><corresp id="cor1">* E-mail: <email>sylviane.lortet@univ-amu.fr</email></corresp><fn fn-type="conflict"><p><bold>Competing Interests: </bold>The authors have declared that no competing interests exist.</p></fn><fn fn-type="con"><p>Conceived and designed the experiments: LK-L PS. Performed the experiments: SL EL NB. Analyzed the data: SL PR CN PS. Contributed reagents/materials/analysis tools: SL NB CN. Wrote the paper: SL LK-L PS.</p></fn></author-notes><pub-date pub-type="collection"><year>2013</year></pub-date><pub-date pub-type="epub"><day>4</day><month>4</month><year>2013</year></pub-date><volume>8</volume><issue>4</issue><elocation-id>e60447</elocation-id><history><date date-type="received"><day>6</day><month>11</month><year>2012</year></date><date date-type="accepted"><day>26</day><month>2</month><year>2013</year></date></history><permissions><copyright-year>2013</copyright-year><copyright-holder>Lortet et al</copyright-holder><license><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</license-p></license></permissions><abstract><p>This study addresses the molecular mechanisms underlying the action of subthalamic nucleus high frequency stimulation (STN-HFS) in the treatment of Parkinson's disease and its interaction with levodopa (L-DOPA), focusing on the striatum. Striatal gene expression profile was assessed in rats with nigral dopamine neuron lesion, either treated or not, using agilent microarrays and qPCR verification. The treatments consisted in anti-akinetic STN-HFS (5 days), chronic L-DOPA treatment inducing dyskinesia (LIDs) or the combination of the two treatments that exacerbated LIDs. STN-HFS modulated 71 striatal genes. The main biological processes associated with the differentially expressed gene products include regulation of growth, of apoptosis and of synaptic transmission, and extracellular region is a major cellular component implicated. In particular, several of these genes have been shown to support survival or differentiation of striatal or of dopaminergic neurons. These results indicate that STN HFS may induce widespread anatomo-functional rearrangements in the striatum and create a molecular environment favorable for neuroprotection and neuroplasticity. STN-HFS and L-DOPA treatment share very few common gene regulation features indicating that the molecular substrates underlying their striatal action are mostly different; among the common effects is the down-regulation of <italic>Adrb1</italic>, which encodes the adrenergic beta-1- receptor, supporting a major role of this receptor in Parkinson's disease. In addition to genes already reported to be associated with LIDs (preprodynorphin, thyrotropin-releasing hormone, metabotropic glutamate receptor 4, cannabinoid receptor 1), the comparison between DOPA and DOPA/HFS identifies immunity-related genes as potential players in L-DOPA side effects.</p></abstract><funding-group><funding-statement>This work was supported by the Centre National de la Recherche Scientifique (CNRS), Aix- Marseille University, and Fédération pour la Recherche sur le Cerveau (FRC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.</funding-statement></funding-group><counts><page-count count="14"></page-count></counts></article-meta></front></pmc></record>Pour manipuler ce document sous Unix (Dilib)
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