Elevated levels of ΔFosB and RGS9 in striatum in Parkinson's disease
Identifieur interne : 003329 ( Main/Exploration ); précédent : 003328; suivant : 003330Elevated levels of ΔFosB and RGS9 in striatum in Parkinson's disease
Auteurs : Poornima K. Tekumalla [États-Unis] ; Frédéric Calon [Canada] ; Zia Rahman [États-Unis] ; Sam Birdi [Canada] ; Ali H. Rajput [Canada] ; Oleh Hornykiewicz [Canada, Autriche] ; Therese Di Paolo [Canada] ; Paul J. Bedard [Canada] ; Eric J. Nestler [États-Unis]Source :
- Biological psychiatry : (1969) [ 0006-3223 ] ; 2001.
Descripteurs français
- Pascal (Inist)
- Wicri :
- topic : Homme.
English descriptors
- KwdEn :
Abstract
Introduction: In the present study, we determined whether certain proteins known to mediate dopamine signaling in striatum show abnormal levels in Parkinson's disease. Methods: Protein levels were assayed by western blotting in samples of caudate nucleus and putumen obtained at autopsy from patients with Parkinson's disease and from control subjects. Levels of several markers of dopaminergic function were also assayed. Results: Levels of the transcription factor ΔFosB and of the G protein modulatory protein RGS9 were both increased in caudate and putamen from patients with Parkinson's disease. Levels of several other proteins were not affected. Interestingly, levels of both ΔFosB and RGS9 correlated inversely with putamen levels of dopamine, dopamine metobolites, and the dopamine transporter. Conclusions: These findings are consistent with observations in laboratory animals, which have demonstrated elevated levels of ΔFosB in striatum after denervation of the midbrain dopamine system, and confirm that similar adaptations in ΔFosB and RGS9 occur in humans with Parkinson's disease. Knowledge of these adaptations can help us understand the changes in striatal function associated with Parkinson's disease and assist in the development of novel treatments.
Affiliations:
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Tekumalla</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Psychiatry, Yale University School of Medicine and Connecticut Mental Health Center</s1><s2>New Haven, Connecticut</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Connecticut</region></placeName></affiliation></author><author><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL), and Faculty of Pharmacy, Laval University</s1><s2>Québec, Qc</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, Qc</wicri:noRegion></affiliation></author><author><name sortKey="Rahman, Zia" sort="Rahman, Zia" uniqKey="Rahman Z" first="Zia" last="Rahman">Zia Rahman</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Psychiatry, Yale University School of Medicine and Connecticut Mental Health Center</s1><s2>New Haven, Connecticut</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Connecticut</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Department of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center</s1><s2>Dallas, Texas</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation></author><author><name sortKey="Birdi, Sam" sort="Birdi, Sam" uniqKey="Birdi S" first="Sam" last="Birdi">Sam Birdi</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Division of Neurology, University of Saskatchewan, Royal University Hospital</s1><s2>Saskatoon, Sk</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Saskatoon, Sk</wicri:noRegion></affiliation></author><author><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H." last="Rajput">Ali H. Rajput</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Division of Neurology, University of Saskatchewan, Royal University Hospital</s1><s2>Saskatoon, Sk</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Saskatoon, Sk</wicri:noRegion></affiliation></author><author><name sortKey="Hornykiewicz, Oleh" sort="Hornykiewicz, Oleh" uniqKey="Hornykiewicz O" first="Oleh" last="Hornykiewicz">Oleh Hornykiewicz</name><affiliation wicri:level="1"><inist:fA14 i1="04"><s1>Division of Neurology, University of Saskatchewan, Royal University Hospital</s1><s2>Saskatoon, Sk</s2><s3>CAN</s3><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Saskatoon, Sk</wicri:noRegion></affiliation><affiliation wicri:level="3"><inist:fA14 i1="05"><s1>Institute for Brain Research, Faculty of Medicine, University of Vienna</s1><s2>Vienna</s2><s3>AUT</s3><sZ>6 aut.</sZ></inist:fA14><country>Autriche</country><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Therese" last="Di Paolo">Therese Di Paolo</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Oncology and Molecular Endocrinology Research Center, Laval University Medical Center (CHUL), and Faculty of Pharmacy, Laval University</s1><s2>Québec, Qc</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>7 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, Qc</wicri:noRegion></affiliation></author><author><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bedard">Paul J. Bedard</name><affiliation wicri:level="1"><inist:fA14 i1="06"><s1>Neuroscience Research Unit, Laval University Medical Center (CHUL)</s1><s2>Québec, Qc</s2><s3>CAN</s3><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, Qc</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="07"><s1>Department of Medicine, Faculty of Medicine, Laval University</s1><s2>Québec, Qc</s2><s3>CAN</s3><sZ>8 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Québec, Qc</wicri:noRegion></affiliation></author><author><name sortKey="Nestler, Eric J" sort="Nestler, Eric J" uniqKey="Nestler E" first="Eric J." last="Nestler">Eric J. Nestler</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Psychiatry, Yale University School of Medicine and Connecticut Mental Health Center</s1><s2>New Haven, Connecticut</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>3 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Connecticut</region></placeName></affiliation><affiliation wicri:level="2"><inist:fA14 i1="03"><s1>Department of Psychiatry and Center for Basic Neuroscience, The University of Texas Southwestern Medical Center</s1><s2>Dallas, Texas</s2><s3>USA</s3><sZ>3 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Texas</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Biological psychiatry : (1969)</title><title level="j" type="abbreviated">Biol. psychiatry : (1969)</title><idno type="ISSN">0006-3223</idno><imprint><date when="2001">2001</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Biological psychiatry : (1969)</title><title level="j" type="abbreviated">Biol. psychiatry : (1969)</title><idno type="ISSN">0006-3223</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Carrier protein</term><term>Caudate nucleus</term><term>Corpus striatum</term><term>Dopamine</term><term>Exploration</term><term>Gene expression</term><term>Human</term><term>Metabolism</term><term>Parkinson disease</term><term>Putamen</term><term>Signal transduction</term><term>Transcription factor RGS9</term><term>Transcription factor ΔFosB</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Parkinson maladie</term><term>Homme</term><term>Transduction signal</term><term>Expression génique</term><term>Dopamine</term><term>Métabolisme</term><term>Corps strié</term><term>Protéine transport</term><term>Exploration</term><term>Noyau caudé</term><term>Putamen</term><term>Facteur transcription ΔFosB</term><term>Facteur transcription RGS9</term></keywords><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Introduction: In the present study, we determined whether certain proteins known to mediate dopamine signaling in striatum show abnormal levels in Parkinson's disease. Methods: Protein levels were assayed by western blotting in samples of caudate nucleus and putumen obtained at autopsy from patients with Parkinson's disease and from control subjects. Levels of several markers of dopaminergic function were also assayed. Results: Levels of the transcription factor ΔFosB and of the G protein modulatory protein RGS9 were both increased in caudate and putamen from patients with Parkinson's disease. Levels of several other proteins were not affected. Interestingly, levels of both ΔFosB and RGS9 correlated inversely with putamen levels of dopamine, dopamine metobolites, and the dopamine transporter. Conclusions: These findings are consistent with observations in laboratory animals, which have demonstrated elevated levels of ΔFosB in striatum after denervation of the midbrain dopamine system, and confirm that similar adaptations in ΔFosB and RGS9 occur in humans with Parkinson's disease. Knowledge of these adaptations can help us understand the changes in striatal function associated with Parkinson's disease and assist in the development of novel treatments.</div></front></TEI><affiliations><list><country><li>Autriche</li><li>Canada</li><li>États-Unis</li></country><region><li>Connecticut</li><li>Texas</li><li>Vienne (Autriche)</li></region><settlement><li>Vienne (Autriche)</li></settlement></list><tree><country name="États-Unis"><region name="Connecticut"><name sortKey="Tekumalla, Poornima K" sort="Tekumalla, Poornima K" uniqKey="Tekumalla P" first="Poornima K." last="Tekumalla">Poornima K. Tekumalla</name></region><name sortKey="Nestler, Eric J" sort="Nestler, Eric J" uniqKey="Nestler E" first="Eric J." last="Nestler">Eric J. Nestler</name><name sortKey="Nestler, Eric J" sort="Nestler, Eric J" uniqKey="Nestler E" first="Eric J." last="Nestler">Eric J. Nestler</name><name sortKey="Rahman, Zia" sort="Rahman, Zia" uniqKey="Rahman Z" first="Zia" last="Rahman">Zia Rahman</name><name sortKey="Rahman, Zia" sort="Rahman, Zia" uniqKey="Rahman Z" first="Zia" last="Rahman">Zia Rahman</name></country><country name="Canada"><noRegion><name sortKey="Calon, Frederic" sort="Calon, Frederic" uniqKey="Calon F" first="Frédéric" last="Calon">Frédéric Calon</name></noRegion><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bedard">Paul J. Bedard</name><name sortKey="Bedard, Paul J" sort="Bedard, Paul J" uniqKey="Bedard P" first="Paul J." last="Bedard">Paul J. Bedard</name><name sortKey="Birdi, Sam" sort="Birdi, Sam" uniqKey="Birdi S" first="Sam" last="Birdi">Sam Birdi</name><name sortKey="Di Paolo, Therese" sort="Di Paolo, Therese" uniqKey="Di Paolo T" first="Therese" last="Di Paolo">Therese Di Paolo</name><name sortKey="Hornykiewicz, Oleh" sort="Hornykiewicz, Oleh" uniqKey="Hornykiewicz O" first="Oleh" last="Hornykiewicz">Oleh Hornykiewicz</name><name sortKey="Rajput, Ali H" sort="Rajput, Ali H" uniqKey="Rajput A" first="Ali H." last="Rajput">Ali H. Rajput</name></country><country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Hornykiewicz, Oleh" sort="Hornykiewicz, Oleh" uniqKey="Hornykiewicz O" first="Oleh" last="Hornykiewicz">Oleh Hornykiewicz</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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