A role for mitogen- and stress-activated kinase 1 in L-DOPA-induced dyskinesia and ΔFosB expression
Identifieur interne : 001500 ( Ncbi/Checkpoint ); précédent : 001499; suivant : 001501A role for mitogen- and stress-activated kinase 1 in L-DOPA-induced dyskinesia and ΔFosB expression
Auteurs : Michael Feyder [Suède] ; Erik Södersten [Suède, Danemark] ; Emanuela Santini [Suède] ; Vincent Vialou [États-Unis, France] ; Quincey C. Laplant [États-Unis] ; Emily L. Watts [États-Unis] ; Giada Spigolon [Suède] ; Klaus Hansen [Danemark] ; Jocelyne Caboche [France] ; Eric Nestler [États-Unis] ; Gilberto Fisone [Suède]Source :
- Biological psychiatry [ 0006-3223 ] ; 2014.
English descriptors
- KwdEn :
- Animals, Antiparkinson Agents (adverse effects), Dyskinesia, Drug-Induced (metabolism), Extracellular Signal-Regulated MAP Kinases (drug effects), Histones (metabolism), Levodopa (adverse effects), Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Neostriatum (drug effects), Neurons (drug effects), Oxidopamine (administration & dosage), Parkinson Disease (complications), Phosphorylation, Proto-Oncogene Proteins c-fos (metabolism), Ribosomal Protein S6 Kinases, 90-kDa (metabolism).
- MESH :
- chemical , administration & dosage : Oxidopamine.
- chemical , adverse effects : Antiparkinson Agents, Levodopa.
- chemical , drug effects : Extracellular Signal-Regulated MAP Kinases.
- complications : Parkinson Disease.
- drug effects : Neostriatum, Neurons.
- metabolism : Dyskinesia, Drug-Induced, Histones, Proto-Oncogene Proteins c-fos, Ribosomal Protein S6 Kinases, 90-kDa.
- Animals, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Phosphorylation.
Abstract
Abnormal regulation of extracellular signal-regulated kinases 1 and 2 (ERK) has been implicated in L-DOPA-induced dyskinesia (LID), a motor complication affecting Parkinson’s disease (PD) patients subjected to standard pharmacotherapy. We examined the involvement in LID of the mitogen- and stress-activated kinase 1 (MSK1), a downstream target of ERK and an important regulator of transcription.
MSK1 knockout (MSK1 KO) mice and ΔFosB- or ΔcJun-overexpressing transgenic mice were lesioned with 6-hydroxydopamine to produce a model of PD and assessed for LID following chronic L-DOPA administration. Biochemical processes were evaluated by Western blotting or immunoflourescence. Histone H3 phosphorylation was analyzed by chromatin immunoprecipitation (ChIP) followed by promotor-specific quantitative PCR.
Genetic inactivation of MSK1 attenuated LID and reduced the phosphorylation of histone H3 at Ser10 in the striatum. ChIP analysis showed that this reduction occurred at the level of the
These results indicate that abnormal regulation of MSK1 contributes to the development of LID and to the concomitant increase in striatal ΔFosB, which may occur via increased histone H3 phosphorylation at the
Url:
DOI: 10.1016/j.biopsych.2014.07.019
PubMed: 25193242
PubMed Central: 4309747
Affiliations:
- Danemark, France, Suède, États-Unis
- Hovedstaden, État de New York, Île-de-France
- Copenhague, Paris
- Université Pierre-et-Marie-Curie
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PMC:4309747Le document en format XML
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Michael" sort="Feyder, Michael" uniqKey="Feyder M" first="Michael" last="Feyder">Michael Feyder</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm</wicri:regionArea><wicri:noRegion>171 77 Stockholm</wicri:noRegion></affiliation></author><author><name sortKey="Sodersten, Erik" sort="Sodersten, Erik" uniqKey="Sodersten E" first="Erik" last="Södersten">Erik Södersten</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm</wicri:regionArea><wicri:noRegion>171 77 Stockholm</wicri:noRegion></affiliation><affiliation wicri:level="3"><nlm:aff id="A2">Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen, Copenhagen</wicri:regionArea><placeName><settlement type="city">Copenhague</settlement><region type="région" nuts="2">Hovedstaden</region></placeName></affiliation></author><author><name sortKey="Santini, Emanuela" sort="Santini, Emanuela" uniqKey="Santini E" first="Emanuela" last="Santini">Emanuela Santini</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm</wicri:regionArea><wicri:noRegion>171 77 Stockholm</wicri:noRegion></affiliation></author><author><name sortKey="Vialou, Vincent" sort="Vialou, Vincent" uniqKey="Vialou V" first="Vincent" last="Vialou">Vincent Vialou</name><affiliation wicri:level="2"><nlm:aff id="A3">Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York</wicri:cityArea></affiliation><affiliation wicri:level="4"><nlm:aff id="A4">INSERM, U952, CNRS UMR 7224, Université Pierre et Marie Curie, Paris 06, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U952, CNRS UMR 7224, Université Pierre et Marie Curie, Paris 06, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Laplant, Quincey C" sort="Laplant, Quincey C" uniqKey="Laplant Q" first="Quincey C." last="Laplant">Quincey C. Laplant</name><affiliation wicri:level="2"><nlm:aff id="A3">Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York</wicri:cityArea></affiliation></author><author><name sortKey="Watts, Emily L" sort="Watts, Emily L" uniqKey="Watts E" first="Emily L." last="Watts">Emily L. Watts</name><affiliation wicri:level="2"><nlm:aff id="A3">Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York</wicri:cityArea></affiliation></author><author><name sortKey="Spigolon, Giada" sort="Spigolon, Giada" uniqKey="Spigolon G" first="Giada" last="Spigolon">Giada Spigolon</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm</wicri:regionArea><wicri:noRegion>171 77 Stockholm</wicri:noRegion></affiliation></author><author><name sortKey="Hansen, Klaus" sort="Hansen, Klaus" uniqKey="Hansen K" first="Klaus" last="Hansen">Klaus Hansen</name><affiliation wicri:level="3"><nlm:aff id="A2">Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen, Copenhagen, Denmark</nlm:aff><country xml:lang="fr">Danemark</country><wicri:regionArea>Biotech Research and Innovation Centre (BRIC) and Centre for Epigenetics, University of Copenhagen, Copenhagen</wicri:regionArea><placeName><settlement type="city">Copenhague</settlement><region type="région" nuts="2">Hovedstaden</region></placeName></affiliation></author><author><name sortKey="Caboche, Jocelyne" sort="Caboche, Jocelyne" uniqKey="Caboche J" first="Jocelyne" last="Caboche">Jocelyne Caboche</name><affiliation wicri:level="4"><nlm:aff id="A4">INSERM, U952, CNRS UMR 7224, Université Pierre et Marie Curie, Paris 06, Paris, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>INSERM, U952, CNRS UMR 7224, Université Pierre et Marie Curie, Paris 06, Paris</wicri:regionArea><placeName><region type="region">Île-de-France</region><region type="old region">Île-de-France</region><settlement type="city">Paris</settlement></placeName><orgName type="university">Université Pierre-et-Marie-Curie</orgName></affiliation></author><author><name sortKey="Nestler, Eric" sort="Nestler, Eric" uniqKey="Nestler E" first="Eric" last="Nestler">Eric Nestler</name><affiliation wicri:level="2"><nlm:aff id="A3">Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029</nlm:aff><country xml:lang="fr">États-Unis</country><placeName><region type="state">État de New York</region></placeName><wicri:cityArea>Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York</wicri:cityArea></affiliation></author><author><name sortKey="Fisone, Gilberto" sort="Fisone, Gilberto" uniqKey="Fisone G" first="Gilberto" last="Fisone">Gilberto Fisone</name><affiliation wicri:level="1"><nlm:aff id="A1">Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm, Sweden</nlm:aff><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Neuroscience, Karolinska Institutet, 171 77 Stockholm</wicri:regionArea><wicri:noRegion>171 77 Stockholm</wicri:noRegion></affiliation></author></analytic><series><title level="j">Biological psychiatry</title><idno type="ISSN">0006-3223</idno><idno type="eISSN">1873-2402</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Antiparkinson Agents (adverse effects)</term><term>Dyskinesia, Drug-Induced (metabolism)</term><term>Extracellular Signal-Regulated MAP Kinases (drug effects)</term><term>Histones (metabolism)</term><term>Levodopa (adverse effects)</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Neostriatum (drug effects)</term><term>Neurons (drug effects)</term><term>Oxidopamine (administration & dosage)</term><term>Parkinson Disease (complications)</term><term>Phosphorylation</term><term>Proto-Oncogene Proteins c-fos (metabolism)</term><term>Ribosomal Protein S6 Kinases, 90-kDa (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Oxidopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="adverse effects" xml:lang="en"><term>Antiparkinson Agents</term><term>Levodopa</term></keywords><keywords scheme="MESH" type="chemical" qualifier="drug effects" xml:lang="en"><term>Extracellular Signal-Regulated MAP Kinases</term></keywords><keywords scheme="MESH" qualifier="complications" xml:lang="en"><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Neostriatum</term><term>Neurons</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Dyskinesia, Drug-Induced</term><term>Histones</term><term>Proto-Oncogene Proteins c-fos</term><term>Ribosomal Protein S6 Kinases, 90-kDa</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Male</term><term>Mice</term><term>Mice, Inbred C57BL</term><term>Mice, Knockout</term><term>Phosphorylation</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><sec id="S1"><title>Background</title><p id="P1">Abnormal regulation of extracellular signal-regulated kinases 1 and 2 (ERK) has been implicated in L-DOPA-induced dyskinesia (LID), a motor complication affecting Parkinson’s disease (PD) patients subjected to standard pharmacotherapy. We examined the involvement in LID of the mitogen- and stress-activated kinase 1 (MSK1), a downstream target of ERK and an important regulator of transcription.</p></sec><sec id="S2"><title>Methods</title><p id="P2">MSK1 knockout (MSK1 KO) mice and ΔFosB- or ΔcJun-overexpressing transgenic mice were lesioned with 6-hydroxydopamine to produce a model of PD and assessed for LID following chronic L-DOPA administration. Biochemical processes were evaluated by Western blotting or immunoflourescence. Histone H3 phosphorylation was analyzed by chromatin immunoprecipitation (ChIP) followed by promotor-specific quantitative PCR.</p></sec><sec id="S3"><title>Results</title><p id="P3">Genetic inactivation of MSK1 attenuated LID and reduced the phosphorylation of histone H3 at Ser10 in the striatum. ChIP analysis showed that this reduction occurred at the level of the <italic>fosB</italic> gene promoter. In line with this observation, the accumulation of ΔFosB produced by chronic L-DOPA was reduced in MSK1 KO. Moreover, inducible overexpression of ΔFosB in striatonigral medium spiny neurons exacerbated dyskinetic behavior, whereas overexpression of ΔcJun, which reduces ΔFosB-dependent transcriptional activation, counteracted LID.</p></sec><sec id="S4"><title>Conclusions</title><p id="P4">These results indicate that abnormal regulation of MSK1 contributes to the development of LID and to the concomitant increase in striatal ΔFosB, which may occur via increased histone H3 phosphorylation at the <italic>fosB</italic> promoter. They also show that accumulation of ΔFosB in striatonigral neurons is causally related to the development of dyskinesia.</p></sec></div></front></TEI><affiliations><list><country><li>Danemark</li><li>France</li><li>Suède</li><li>États-Unis</li></country><region><li>Hovedstaden</li><li>État de New York</li><li>Île-de-France</li></region><settlement><li>Copenhague</li><li>Paris</li></settlement><orgName><li>Université Pierre-et-Marie-Curie</li></orgName></list><tree><country name="Suède"><noRegion><name sortKey="Feyder, Michael" sort="Feyder, Michael" uniqKey="Feyder M" first="Michael" last="Feyder">Michael Feyder</name></noRegion><name sortKey="Fisone, Gilberto" sort="Fisone, Gilberto" uniqKey="Fisone G" first="Gilberto" last="Fisone">Gilberto Fisone</name><name sortKey="Santini, Emanuela" sort="Santini, Emanuela" uniqKey="Santini E" first="Emanuela" last="Santini">Emanuela Santini</name><name sortKey="Sodersten, Erik" sort="Sodersten, Erik" uniqKey="Sodersten E" first="Erik" last="Södersten">Erik Södersten</name><name sortKey="Spigolon, Giada" sort="Spigolon, Giada" uniqKey="Spigolon G" first="Giada" last="Spigolon">Giada Spigolon</name></country><country name="Danemark"><region name="Hovedstaden"><name sortKey="Sodersten, Erik" sort="Sodersten, Erik" uniqKey="Sodersten E" first="Erik" last="Södersten">Erik Södersten</name></region><name sortKey="Hansen, Klaus" sort="Hansen, Klaus" uniqKey="Hansen K" first="Klaus" last="Hansen">Klaus Hansen</name></country><country name="États-Unis"><region name="État de New York"><name sortKey="Vialou, Vincent" sort="Vialou, Vincent" uniqKey="Vialou V" first="Vincent" last="Vialou">Vincent Vialou</name></region><name sortKey="Laplant, Quincey C" sort="Laplant, Quincey C" uniqKey="Laplant Q" first="Quincey C." last="Laplant">Quincey C. Laplant</name><name sortKey="Nestler, Eric" sort="Nestler, Eric" uniqKey="Nestler E" first="Eric" last="Nestler">Eric Nestler</name><name sortKey="Watts, Emily L" sort="Watts, Emily L" uniqKey="Watts E" first="Emily L." last="Watts">Emily L. Watts</name></country><country name="France"><region name="Île-de-France"><name sortKey="Vialou, Vincent" sort="Vialou, Vincent" uniqKey="Vialou V" first="Vincent" last="Vialou">Vincent Vialou</name></region><name sortKey="Caboche, Jocelyne" sort="Caboche, Jocelyne" uniqKey="Caboche J" first="Jocelyne" last="Caboche">Jocelyne Caboche</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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