Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease
Identifieur interne : 001938 ( Main/Exploration ); précédent : 001937; suivant : 001939Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease
Auteurs : Ramachandiran Nandhagopal [Canada] ; Lisa Kuramoto [Canada] ; Michael Schulzer [Canada] ; Edwin Mak [Canada] ; Jacqueline Cragg [Canada] ; Jess Mckenzie [Canada] ; Siobhan Mccormick [Canada] ; Thomas J. Ruth [Canada] ; Vesna Sossi [Canada] ; Raul De La Fuente-Fernandez [Canada] ; A. Jon Stoessl [Canada]Source :
- Brain [ 0006-8950 ] ; 2011.
Descripteurs français
- Pascal (Inist)
English descriptors
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Abstract
Parkinson's disease is a relentlessly progressive neurodegenerative disease. Breakdown of compensatory mechanisms influencing putaminal dopamine processing could contribute to the progressive motor symptoms. We studied a cohort of 78 subjects (at baseline) with sporadic Parkinson's disease and 35 healthy controls with multi-tracer positron emission tomography scans to investigate the evolution of adaptive mechanisms influencing striatal dopamine processing in Parkinson's disease progression. Presynaptic dopaminergic integrity was assessed with three radioligands: (i) [11C](±)dihydrotetrabenazine, to estimate the density of vesicular monoamine transporter type 2; (ii) [11C]d-threo-methylphenidate, to label the dopamine transporter; and (iii) 6-[18F]fluoro-L-DOPA, to assess the activity of aromatic amino acid decarboxylase and storage of 6-[18F]-fluorodopamine in synaptic vesicles. The subjects with Parkinson's disease and the healthy controls underwent positron emission tomography scans at the initial visit and after 4 and 8 years of follow-up. Non-linear multivariate regression analyses with random effects were utilized to model the longitudinal changes in tracer values in the putamen standardized relative to normal controls. We found evidence for possible upregulation of dopamine synthesis and downregulation of dopamine transporter in the more severely affected putamen in the early stage of Parkinson's disease. The standardized 6-[18F]fluoro-L-DOPA and [11C]d-threo-methylphenidate values tended to approach [11C](±)dihydrotetrabenazine values in the putamen in later stages of disease (i.e. for [11C](±)dihydrotetrabenazine values <25% of normal), when the rates of decline in the positron emission tomography measurements were similar for all the markers. Our data suggest that compensatory mechanisms decline as Parkinson's disease progresses. This breakdown of compensatory strategies in the putamen could contribute to the progression of motor symptoms in advanced disease.
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease</title><author><name sortKey="Nandhagopal, Ramachandiran" sort="Nandhagopal, Ramachandiran" uniqKey="Nandhagopal R" first="Ramachandiran" last="Nandhagopal">Ramachandiran Nandhagopal</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Kuramoto, Lisa" sort="Kuramoto, Lisa" uniqKey="Kuramoto L" first="Lisa" last="Kuramoto">Lisa Kuramoto</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Mak, Edwin" sort="Mak, Edwin" uniqKey="Mak E" first="Edwin" last="Mak">Edwin Mak</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Cragg, Jacqueline" sort="Cragg, Jacqueline" uniqKey="Cragg J" first="Jacqueline" last="Cragg">Jacqueline Cragg</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Mckenzie, Jess" sort="Mckenzie, Jess" uniqKey="Mckenzie J" first="Jess" last="Mckenzie">Jess Mckenzie</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Mccormick, Siobhan" sort="Mccormick, Siobhan" uniqKey="Mccormick S" first="Siobhan" last="Mccormick">Siobhan Mccormick</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Ruth, Thomas J" sort="Ruth, Thomas J" uniqKey="Ruth T" first="Thomas J." last="Ruth">Thomas J. Ruth</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>TRIUMF, University of British Columbia, Wesbrook Mall</s1><s2>Vancouver, BC V6T 2A3</s2><s3>CAN</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2A3</wicri:noRegion></affiliation></author><author><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>TRIUMF, University of British Columbia, Wesbrook Mall</s1><s2>Vancouver, BC V6T 2A3</s2><s3>CAN</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2A3</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Physics and Astronomy, University of British Columbia</s1><s2>Vancouver, BC V6T 1Z1</s2><s3>CAN</s3><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 1Z1</wicri:noRegion></affiliation></author><author><name sortKey="De La Fuente Fernandez, Raul" sort="De La Fuente Fernandez, Raul" uniqKey="De La Fuente Fernandez R" first="Raul" last="De La Fuente-Fernandez">Raul De La Fuente-Fernandez</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Jon Stoessl, A" sort="Jon Stoessl, A" uniqKey="Jon Stoessl A" first="A." last="Jon Stoessl">A. Jon Stoessl</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">11-0502376</idno><date when="2011">2011</date><idno type="stanalyst">PASCAL 11-0502376 INIST</idno><idno type="RBID">Pascal:11-0502376</idno><idno type="wicri:Area/PascalFrancis/Corpus">000264</idno><idno type="wicri:Area/PascalFrancis/Curation">000999</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000257</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000257</idno><idno type="wicri:doubleKey">0006-8950:2011:Nandhagopal R:longitudinal:evolution:of</idno><idno type="wicri:Area/Main/Merge">001A32</idno><idno type="wicri:Area/Main/Curation">001938</idno><idno type="wicri:Area/Main/Exploration">001938</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease</title><author><name sortKey="Nandhagopal, Ramachandiran" sort="Nandhagopal, Ramachandiran" uniqKey="Nandhagopal R" first="Ramachandiran" last="Nandhagopal">Ramachandiran Nandhagopal</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Kuramoto, Lisa" sort="Kuramoto, Lisa" uniqKey="Kuramoto L" first="Lisa" last="Kuramoto">Lisa Kuramoto</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Mak, Edwin" sort="Mak, Edwin" uniqKey="Mak E" first="Edwin" last="Mak">Edwin Mak</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Cragg, Jacqueline" sort="Cragg, Jacqueline" uniqKey="Cragg J" first="Jacqueline" last="Cragg">Jacqueline Cragg</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Mckenzie, Jess" sort="Mckenzie, Jess" uniqKey="Mckenzie J" first="Jess" last="Mckenzie">Jess Mckenzie</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Mccormick, Siobhan" sort="Mccormick, Siobhan" uniqKey="Mccormick S" first="Siobhan" last="Mccormick">Siobhan Mccormick</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Ruth, Thomas J" sort="Ruth, Thomas J" uniqKey="Ruth T" first="Thomas J." last="Ruth">Thomas J. Ruth</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>TRIUMF, University of British Columbia, Wesbrook Mall</s1><s2>Vancouver, BC V6T 2A3</s2><s3>CAN</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2A3</wicri:noRegion></affiliation></author><author><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>TRIUMF, University of British Columbia, Wesbrook Mall</s1><s2>Vancouver, BC V6T 2A3</s2><s3>CAN</s3><sZ>8 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2A3</wicri:noRegion></affiliation><affiliation wicri:level="1"><inist:fA14 i1="03"><s1>Department of Physics and Astronomy, University of British Columbia</s1><s2>Vancouver, BC V6T 1Z1</s2><s3>CAN</s3><sZ>9 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 1Z1</wicri:noRegion></affiliation></author><author><name sortKey="De La Fuente Fernandez, Raul" sort="De La Fuente Fernandez, Raul" uniqKey="De La Fuente Fernandez R" first="Raul" last="De La Fuente-Fernandez">Raul De La Fuente-Fernandez</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author><author><name sortKey="Jon Stoessl, A" sort="Jon Stoessl, A" uniqKey="Jon Stoessl A" first="A." last="Jon Stoessl">A. Jon Stoessl</name><affiliation wicri:level="1"><inist:fA14 i1="01"><s1>Pacific Parkinson's Research Centre, University of British Columbia and Vancouver Coastal Health, 2221 Wesbrook Mall</s1><s2>Vancouver, BC V6T 2B5</s2><s3>CAN</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>10 aut.</sZ><sZ>11 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver, BC V6T 2B5</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Brain</title><title level="j" type="abbreviated">Brain</title><idno type="ISSN">0006-8950</idno><imprint><date when="2011">2011</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Brain</title><title level="j" type="abbreviated">Brain</title><idno type="ISSN">0006-8950</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dopamine</term><term>Emission tomography</term><term>Evolution</term><term>Motor system disorder</term><term>Nervous system diseases</term><term>Parkinson disease</term><term>Positron emission tomography</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Trouble moteur</term><term>Pathologie du système nerveux</term><term>Evolution</term><term>Dopamine</term><term>Tomoscintigraphie</term><term>Tomographie par émission de positons</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Parkinson's disease is a relentlessly progressive neurodegenerative disease. Breakdown of compensatory mechanisms influencing putaminal dopamine processing could contribute to the progressive motor symptoms. We studied a cohort of 78 subjects (at baseline) with sporadic Parkinson's disease and 35 healthy controls with multi-tracer positron emission tomography scans to investigate the evolution of adaptive mechanisms influencing striatal dopamine processing in Parkinson's disease progression. Presynaptic dopaminergic integrity was assessed with three radioligands: (i) [<sup>11</sup>C](±)dihydrotetrabenazine, to estimate the density of vesicular monoamine transporter type 2; (ii) [<sup>11</sup>C]d-threo-methylphenidate, to label the dopamine transporter; and (iii) 6-[<sup>18</sup>F]fluoro-L-DOPA, to assess the activity of aromatic amino acid decarboxylase and storage of 6-[<sup>18</sup>F]-fluorodopamine in synaptic vesicles. The subjects with Parkinson's disease and the healthy controls underwent positron emission tomography scans at the initial visit and after 4 and 8 years of follow-up. Non-linear multivariate regression analyses with random effects were utilized to model the longitudinal changes in tracer values in the putamen standardized relative to normal controls. We found evidence for possible upregulation of dopamine synthesis and downregulation of dopamine transporter in the more severely affected putamen in the early stage of Parkinson's disease. The standardized 6-[<sup>18</sup>F]fluoro-L-DOPA and [<sup>11</sup>C]d-threo-methylphenidate values tended to approach [<sup>11</sup>C](±)dihydrotetrabenazine values in the putamen in later stages of disease (i.e. for [<sup>11</sup>C](±)dihydrotetrabenazine values <25% of normal), when the rates of decline in the positron emission tomography measurements were similar for all the markers. Our data suggest that compensatory mechanisms decline as Parkinson's disease progresses. This breakdown of compensatory strategies in the putamen could contribute to the progression of motor symptoms in advanced disease.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="Nandhagopal, Ramachandiran" sort="Nandhagopal, Ramachandiran" uniqKey="Nandhagopal R" first="Ramachandiran" last="Nandhagopal">Ramachandiran Nandhagopal</name></noRegion><name sortKey="Cragg, Jacqueline" sort="Cragg, Jacqueline" uniqKey="Cragg J" first="Jacqueline" last="Cragg">Jacqueline Cragg</name><name sortKey="De La Fuente Fernandez, Raul" sort="De La Fuente Fernandez, Raul" uniqKey="De La Fuente Fernandez R" first="Raul" last="De La Fuente-Fernandez">Raul De La Fuente-Fernandez</name><name sortKey="Jon Stoessl, A" sort="Jon Stoessl, A" uniqKey="Jon Stoessl A" first="A." last="Jon Stoessl">A. Jon Stoessl</name><name sortKey="Kuramoto, Lisa" sort="Kuramoto, Lisa" uniqKey="Kuramoto L" first="Lisa" last="Kuramoto">Lisa Kuramoto</name><name sortKey="Mak, Edwin" sort="Mak, Edwin" uniqKey="Mak E" first="Edwin" last="Mak">Edwin Mak</name><name sortKey="Mccormick, Siobhan" sort="Mccormick, Siobhan" uniqKey="Mccormick S" first="Siobhan" last="Mccormick">Siobhan Mccormick</name><name sortKey="Mckenzie, Jess" sort="Mckenzie, Jess" uniqKey="Mckenzie J" first="Jess" last="Mckenzie">Jess Mckenzie</name><name sortKey="Ruth, Thomas J" sort="Ruth, Thomas J" uniqKey="Ruth T" first="Thomas J." last="Ruth">Thomas J. Ruth</name><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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|type= RBID
|clé= Pascal:11-0502376
|texte= Longitudinal evolution of compensatory changes in striatal dopamine processing in Parkinson's disease
}}
| This area was generated with Dilib version V0.6.29. |  |