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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<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">État de New York</region>
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<author><name sortKey="Spigolon, Giada" sort="Spigolon, Giada" uniqKey="Spigolon G" first="Giada" last="Spigolon">Giada Spigolon</name>
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<country xml:lang="fr">Suède</country>
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<author><name sortKey="Hansen, Klaus" sort="Hansen, Klaus" uniqKey="Hansen K" first="Klaus" last="Hansen">Klaus Hansen</name>
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<author><name sortKey="Caboche, Jocelyne" sort="Caboche, Jocelyne" uniqKey="Caboche J" first="Jocelyne" last="Caboche">Jocelyne Caboche</name>
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<country xml:lang="fr">France</country>
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<country xml:lang="fr">États-Unis</country>
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<country xml:lang="fr">Suède</country>
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<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>
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<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>
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