Progressive changes of pre‐ and post‐synaptic dopaminergic biomarkers in conscious MPTP‐treated cynomolgus monkeys measured by positronemission tomography
Identifieur interne : 000F78 ( Main/Exploration ); précédent : 000F77; suivant : 000F79Progressive changes of pre‐ and post‐synaptic dopaminergic biomarkers in conscious MPTP‐treated cynomolgus monkeys measured by positronemission tomography
Auteurs : Yuji Nagai [Japon] ; Shigeru Obayashi [Japon] ; Kiyoshi Ando [Japon] ; Motoki Inaji [Japon] ; Jun Maeda [Japon] ; Takashi Okauchi [Japon] ; Hiroshi Ito [Japon] ; Tetsuya Suhara [Japon]Source :
- Synapse [ 0887-4476 ] ; 2007-10.
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Abstract
Positron emission tomography (PET) is a useful technique for the consecutive investigation of the relationship between changes in neurotransmission biomarkers and behavioral signs in animal models of Parkinson's disease (PD). In this study, we aimed to investigate the threshold of dopamine (DA) neuron damage for the appearance of tremor by observing the longitudinal changes of pre‐ and post‐synaptic DA biomarkers in awake monkeys using PET with multiple tracers. Three cynomolgus monkeys were treated with MPTP every 3–6 weeks until tremor was observed. Brain uptake of [11C]PE2I, [β‐11C]DOPA, and [11C]raclopride for DA transporter (DAT), DOPA utilization, and DA D2 receptor were measured using PET as a single set in awake condition. Sets of PET scans were repeated in parallel with continuous behavioral estimation. The pre‐synaptic biomarkers of DA neuron in the striatum decreased [11C]PE2I binding and [β‐11C]DOPA uptake in an MPTP dose‐dependent manner. Tremor was not observed until striatal [11C]PE2I binding was reduced to about 15% of the pretreatment level and [β‐11C]DOPA uptake was reduced to about 34%. DA D2 receptor measured by [11C]raclopride was not significantly changed throughout the experiment. Our results revealed that it is possible to quantitatively define the threshold of the onset of behavioral PD signs by monitoring spontaneous motor activity, and in vivo PET with DAT marker can be a biomarker for early diagnosis at the presymptomatic stage of PD and for high‐risk groups. Synapse 61:809–819, 2007. © 2007 Wiley‐Liss, Inc.
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DOI: 10.1002/syn.20431
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uniqKey="Okauchi T" first="Takashi" last="Okauchi">Takashi Okauchi</name></author><author><name sortKey="Ito, Hiroshi" sort="Ito, Hiroshi" uniqKey="Ito H" first="Hiroshi" last="Ito">Hiroshi Ito</name></author><author><name sortKey="Suhara, Tetsuya" sort="Suhara, Tetsuya" uniqKey="Suhara T" first="Tetsuya" last="Suhara">Tetsuya Suhara</name></author></titleStmt><publicationStmt><idno type="wicri:source">ISTEX</idno><idno type="RBID">ISTEX:881BBA5D63463BC2292E632E40D4B877D0C1EEAB</idno><date when="2007" year="2007">2007</date><idno type="doi">10.1002/syn.20431</idno><idno type="url">https://api.istex.fr/document/881BBA5D63463BC2292E632E40D4B877D0C1EEAB/fulltext/pdf</idno><idno type="wicri:Area/Main/Corpus">002E07</idno><idno type="wicri:Area/Main/Curation">002A24</idno><idno type="wicri:Area/Main/Exploration">000F78</idno></publicationStmt><sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Progressive changes of pre‐ and post‐synaptic dopaminergic biomarkers in 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sort="Ito, Hiroshi" uniqKey="Ito H" first="Hiroshi" last="Ito">Hiroshi Ito</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Neuroimaging, Molecular Imaging Center, National Institute of Radiological Sciences, Inage‐ku, Chiba 263‐8555</wicri:regionArea><wicri:noRegion>Chiba 263‐8555</wicri:noRegion></affiliation></author><author><name sortKey="Suhara, Tetsuya" sort="Suhara, Tetsuya" uniqKey="Suhara T" first="Tetsuya" last="Suhara">Tetsuya Suhara</name><affiliation wicri:level="1"><country xml:lang="fr">Japon</country><wicri:regionArea>Department of Molecular Neuroimaging, Molecular Imaging Center, National Institute of Radiological Sciences, Inage‐ku, Chiba 263‐8555</wicri:regionArea><wicri:noRegion>Chiba 263‐8555</wicri:noRegion></affiliation></author></analytic><monogr></monogr><series><title level="j">Synapse</title><title level="j" type="abbrev">Synapse</title><idno type="ISSN">0887-4476</idno><idno 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xml:lang="en">Positron emission tomography (PET) is a useful technique for the consecutive investigation of the relationship between changes in neurotransmission biomarkers and behavioral signs in animal models of Parkinson's disease (PD). In this study, we aimed to investigate the threshold of dopamine (DA) neuron damage for the appearance of tremor by observing the longitudinal changes of pre‐ and post‐synaptic DA biomarkers in awake monkeys using PET with multiple tracers. Three cynomolgus monkeys were treated with MPTP every 3–6 weeks until tremor was observed. Brain uptake of [11C]PE2I, [β‐11C]DOPA, and [11C]raclopride for DA transporter (DAT), DOPA utilization, and DA D2 receptor were measured using PET as a single set in awake condition. Sets of PET scans were repeated in parallel with continuous behavioral estimation. The pre‐synaptic biomarkers of DA neuron in the striatum decreased [11C]PE2I binding and [β‐11C]DOPA uptake in an MPTP dose‐dependent manner. Tremor was not observed until striatal [11C]PE2I binding was reduced to about 15% of the pretreatment level and [β‐11C]DOPA uptake was reduced to about 34%. DA D2 receptor measured by [11C]raclopride was not significantly changed throughout the experiment. Our results revealed that it is possible to quantitatively define the threshold of the onset of behavioral PD signs by monitoring spontaneous motor activity, and in vivo PET with DAT marker can be a biomarker for early diagnosis at the presymptomatic stage of PD and for high‐risk groups. Synapse 61:809–819, 2007. © 2007 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>Japon</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Nagai, Yuji" sort="Nagai, Yuji" uniqKey="Nagai Y" first="Yuji" last="Nagai">Yuji Nagai</name></noRegion><name sortKey="Ando, Kiyoshi" sort="Ando, Kiyoshi" uniqKey="Ando K" first="Kiyoshi" last="Ando">Kiyoshi Ando</name><name sortKey="Ando, Kiyoshi" sort="Ando, Kiyoshi" uniqKey="Ando K" first="Kiyoshi" last="Ando">Kiyoshi Ando</name><name sortKey="Inaji, Motoki" sort="Inaji, Motoki" uniqKey="Inaji M" first="Motoki" last="Inaji">Motoki Inaji</name><name sortKey="Ito, Hiroshi" sort="Ito, Hiroshi" uniqKey="Ito H" first="Hiroshi" last="Ito">Hiroshi Ito</name><name sortKey="Maeda, Jun" sort="Maeda, Jun" uniqKey="Maeda J" first="Jun" last="Maeda">Jun Maeda</name><name sortKey="Obayashi, Shigeru" sort="Obayashi, Shigeru" uniqKey="Obayashi S" first="Shigeru" last="Obayashi">Shigeru Obayashi</name><name sortKey="Okauchi, Takashi" sort="Okauchi, Takashi" uniqKey="Okauchi T" first="Takashi" last="Okauchi">Takashi Okauchi</name><name sortKey="Suhara, Tetsuya" sort="Suhara, Tetsuya" uniqKey="Suhara T" first="Tetsuya" last="Suhara">Tetsuya Suhara</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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