Dopamine Turnover Increases in Asymptomatic LRRK2 Mutations Carriers
Identifieur interne : 001E58 ( Main/Merge ); précédent : 001E57; suivant : 001E59Dopamine Turnover Increases in Asymptomatic LRRK2 Mutations Carriers
Auteurs : Vesna Sossi [Canada] ; Raul De La Fuente-Fernandez [Canada] ; Ramachandiran Nandhagopal [Canada] ; Michael Schulzer [Canada] ; Jessamyn Mckenzie [Canada] ; Thomas J. Ruth [Canada] ; Jan O. Aasly [Norvège] ; Matthew J. Farrer [États-Unis] ; Zbigniew K. Wszolek [États-Unis] ; Jon A. Stoessl [Canada]Source :
- Movement disorders [ 0885-3185 ] ; 2010.
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- Pascal (Inist)
English descriptors
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Abstract
Increase in dopamine (DA) turnover was found to occur early in symptomatic Parkinson's disease (PD) and to be functionally related to the dopamine transporter (DAT). The objectives of this study were to examine changes in DA turnover in the asymptomatic PD phase; to compare them with changes in other dopaminergic markers, and to investigate a possible relationship between DAT and DA turnover. Eight subjects from families at increased risk of PD due to LRRK2 mutation were investigated. Positron emission tomography imaging was performed with: 18F-fluorodopa to determine the effective DA distribution volume (EDV), the inverse of DA turnover, and the DA uptake rate Kocc, a marker of DA synthesis and storage; C-methylphenidate (MP, a DAT marker) and 11C-dihydrotetrabenazine (DTBZ, a VMAT2 marker) to estimate the binding potentials BPND_MP and BPND_DTBZ. On average, EDV showed the largest reduction from age-matched control values (42%) followed by BPND_MP (23%) and BPND_DTBZ (17%), whereas Kocc remained in the normal range for all subjects. No correlation was found between EDV and any other marker. DA turnover was found to be elevated in asymptomatic mutation carriers at increased risk of PD. Such change was determined to be larger than and statistically independent from changes observed with the other markers. These results support a compensatory role of increased DA turnover in presymptomatic disease and indicate that at this stage, in contrast to the symptomatic PD phase, increased turnover is not related to DAT.
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Farrer</name><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Wszolek, Zbigniew K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K." last="Wszolek">Zbigniew K. Wszolek</name><affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Department of Neurology, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Stoessl, Jon A" sort="Stoessl, Jon A" uniqKey="Stoessl J" first="Jon A." last="Stoessl">Jon A. Stoessl</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Pacific Parkinson's Research Centre</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Pacific Parkinson's Research Centre</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">11-0065108</idno><date when="2010">2010</date><idno type="stanalyst">PASCAL 11-0065108 INIST</idno><idno type="RBID">Pascal:11-0065108</idno><idno type="wicri:Area/PascalFrancis/Corpus">000351</idno><idno type="wicri:Area/PascalFrancis/Curation">000912</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000368</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000368</idno><idno type="wicri:doubleKey">0885-3185:2010:Sossi V:dopamine:turnover:increases</idno><idno type="wicri:Area/Main/Merge">001E58</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Dopamine Turnover Increases in Asymptomatic LRRK2 Mutations Carriers</title><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="01"><s1>Department of Physics and Astronomy, University of British Columbia</s1><s2>Vancouver British Columbia</s2><s3>CAN</s3><sZ>1 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Vancouver British Columbia</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="02"><s1>Pacific Parkinson's Research Centre</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Pacific Parkinson's Research Centre</wicri:noRegion></affiliation></author><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="02"><s1>Pacific Parkinson's Research Centre</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Pacific Parkinson's Research Centre</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="02"><s1>Pacific Parkinson's Research Centre</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Pacific Parkinson's Research Centre</wicri:noRegion></affiliation></author><author><name sortKey="Mckenzie, Jessamyn" sort="Mckenzie, Jessamyn" uniqKey="Mckenzie J" first="Jessamyn" last="Mckenzie">Jessamyn Mckenzie</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Pacific Parkinson's Research Centre</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Pacific Parkinson's Research Centre</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="03"><s1>TRIUMF</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>6 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>TRIUMF</wicri:noRegion></affiliation></author><author><name sortKey="Aasly, Jan O" sort="Aasly, Jan O" uniqKey="Aasly J" first="Jan O." last="Aasly">Jan O. Aasly</name><affiliation wicri:level="3"><inist:fA14 i1="04"><s1>Department of Neuroscience and Neurology, NTNU</s1><s2>Trondheim</s2><s3>NOR</s3><sZ>7 aut.</sZ></inist:fA14><country>Norvège</country><placeName><settlement type="city">Trondheim</settlement><region type="région" nuts="2">Trøndelag</region></placeName></affiliation></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J." last="Farrer">Matthew J. Farrer</name><affiliation wicri:level="2"><inist:fA14 i1="05"><s1>Department of Neuroscience, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Wszolek, Zbigniew K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K." last="Wszolek">Zbigniew K. Wszolek</name><affiliation wicri:level="2"><inist:fA14 i1="06"><s1>Department of Neurology, Mayo Clinic</s1><s2>Jacksonville, Florida</s2><s3>USA</s3><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Floride</region></placeName></affiliation></author><author><name sortKey="Stoessl, Jon A" sort="Stoessl, Jon A" uniqKey="Stoessl J" first="Jon A." last="Stoessl">Jon A. Stoessl</name><affiliation wicri:level="1"><inist:fA14 i1="02"><s1>Pacific Parkinson's Research Centre</s1><s2>Vancouver, British Columbia</s2><s3>CAN</s3><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>10 aut.</sZ></inist:fA14><country>Canada</country><wicri:noRegion>Pacific Parkinson's Research Centre</wicri:noRegion></affiliation></author></analytic><series><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno><imprint><date when="2010">2010</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Movement disorders</title><title level="j" type="abbreviated">Mov. disord.</title><idno type="ISSN">0885-3185</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Asymptomatic</term><term>Carrier</term><term>Dopamine</term><term>Mutation</term><term>Nervous system diseases</term><term>Parkinson disease</term><term>Positron emission tomography</term><term>Turnover</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Maladie de Parkinson</term><term>Pathologie du système nerveux</term><term>Dopamine</term><term>Turnover</term><term>Asymptomatique</term><term>Mutation</term><term>Porteur</term><term>Tomographie par émission de positons</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Increase in dopamine (DA) turnover was found to occur early in symptomatic Parkinson's disease (PD) and to be functionally related to the dopamine transporter (DAT). The objectives of this study were to examine changes in DA turnover in the asymptomatic PD phase; to compare them with changes in other dopaminergic markers, and to investigate a possible relationship between DAT and DA turnover. Eight subjects from families at increased risk of PD due to LRRK2 mutation were investigated. Positron emission tomography imaging was performed with: <sup>18</sup>F-fluorodopa to determine the effective DA distribution volume (EDV), the inverse of DA turnover, and the DA uptake rate K<sub>occ</sub>, a marker of DA synthesis and storage; C-methylphenidate (MP, a DAT marker) and <sup>11</sup>C-dihydrotetrabenazine (DTBZ, a VMAT2 marker) to estimate the binding potentials BP<sub>ND_MP</sub> and BP<sub>ND_DTBZ</sub>. On average, EDV showed the largest reduction from age-matched control values (42%) followed by BP<sub>ND_MP</sub> (23%) and BP<sub>ND_DTBZ</sub> (17%), whereas K<sub>occ</sub> remained in the normal range for all subjects. No correlation was found between EDV and any other marker. DA turnover was found to be elevated in asymptomatic mutation carriers at increased risk of PD. Such change was determined to be larger than and statistically independent from changes observed with the other markers. These results support a compensatory role of increased DA turnover in presymptomatic disease and indicate that at this stage, in contrast to the symptomatic PD phase, increased turnover is not related to DAT.</div></front></TEI><affiliations><list><country><li>Canada</li><li>Norvège</li><li>États-Unis</li></country><region><li>Floride</li><li>Trøndelag</li></region><settlement><li>Trondheim</li></settlement></list><tree><country name="Canada"><noRegion><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name></noRegion><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="Mckenzie, Jessamyn" sort="Mckenzie, Jessamyn" uniqKey="Mckenzie J" first="Jessamyn" last="Mckenzie">Jessamyn Mckenzie</name><name sortKey="Nandhagopal, Ramachandiran" sort="Nandhagopal, Ramachandiran" uniqKey="Nandhagopal R" first="Ramachandiran" last="Nandhagopal">Ramachandiran Nandhagopal</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="Stoessl, Jon A" sort="Stoessl, Jon A" uniqKey="Stoessl J" first="Jon A." last="Stoessl">Jon A. Stoessl</name></country><country name="Norvège"><region name="Trøndelag"><name sortKey="Aasly, Jan O" sort="Aasly, Jan O" uniqKey="Aasly J" first="Jan O." last="Aasly">Jan O. Aasly</name></region></country><country name="États-Unis"><region name="Floride"><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J." last="Farrer">Matthew J. Farrer</name></region><name sortKey="Wszolek, Zbigniew K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K." last="Wszolek">Zbigniew K. Wszolek</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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