In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease.
Identifieur interne : 000093 ( Ncbi/Checkpoint ); précédent : 000092; suivant : 000094In vivo positron emission tomographic evidence for compensatory changes in presynaptic dopaminergic nerve terminals in Parkinson's disease.
Auteurs : C S Lee [Canada] ; A. Samii ; V. Sossi ; T J Ruth ; M. Schulzer ; J E Holden ; J. Wudel ; P K Pal ; R. De La Fuente-Fernandez ; D B Calne ; A J StoesslSource :
- Annals of neurology [ 0364-5134 ] ; 2000.
English descriptors
- KwdEn :
- Aged, Carbon Radioisotopes, Carrier Proteins (metabolism), Corpus Striatum (diagnostic imaging), Corpus Striatum (metabolism), Dopamine (metabolism), Dopamine Plasma Membrane Transport Proteins, Down-Regulation (physiology), Fluorine Radioisotopes, Homovanillic Acid (metabolism), Humans, Membrane Glycoproteins, Membrane Transport Proteins, Middle Aged, Nerve Tissue Proteins, Parkinson Disease (diagnostic imaging), Parkinson Disease (metabolism), Presynaptic Terminals (metabolism), Tetrabenazine (analogs & derivatives), Tomography, Emission-Computed.
- MESH :
- chemical , analogs & derivatives : Tetrabenazine.
- chemical , metabolism : Carrier Proteins, Dopamine, Homovanillic Acid.
- chemical : Carbon Radioisotopes, Dopamine Plasma Membrane Transport Proteins, Fluorine Radioisotopes, Membrane Glycoproteins, Membrane Transport Proteins, Nerve Tissue Proteins.
- diagnostic imaging : Corpus Striatum, Parkinson Disease.
- metabolism : Corpus Striatum, Parkinson Disease, Presynaptic Terminals.
- physiology : Down-Regulation.
- Aged, Humans, Middle Aged, Tomography, Emission-Computed.
Abstract
Clinical symptoms of Parkinson's disease (PD) do not manifest until dopamine (DA) neuronal loss reaches a symptomatic threshold. To explore the mechanisms of functional compensation that occur in presynaptic DA nerve terminals in PD, we compared striatal positron emission tomographic (PET) measurements by using [11C]dihydrotetrabenazine ([11C]DTBZ; labeling the vesicular monoamine transporter type 2), [11C]methylphenidate (labeling the plasma membrane DA transporter), and [18F]dopa (reflecting synthesis and storage of DA). Three consecutive PET scans were performed in three-dimensional mode by using each tracer on 35 patients and 16 age-matched, normal controls. PET measurements by the three tracers were compared between subgroups of earlier and later stages of PD, between drug-naive and drug-treated subgroups of PD, and between subregions of the parkinsonian striatum. The quantitative relationships of [18F]dopa and [11]DTBZ, and of [11C]methylphenidate and [11C]DTBZ, were compared between the PD and the normal control subjects. We found that [18F]dopa Ki was reduced less than the binding potential (Bmax/Kd) for [11C]DTBZ in the parkinsonian striatum, whereas the [11C]methylphenidate binding potential was reduced more than [11C]DTBZ binding potential. These observations suggest that the activity of aromatic L-amino acid decarboxylase is up-regulated, whereas the plasma membrane DA transporter is down-regulated in the striatum of patients with PD.
PubMed: 10762161
Affiliations:
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Sossi</name></author><author><name sortKey="Ruth, T J" sort="Ruth, T J" uniqKey="Ruth T" first="T J" last="Ruth">T J Ruth</name></author><author><name sortKey="Schulzer, M" sort="Schulzer, M" uniqKey="Schulzer M" first="M" last="Schulzer">M. Schulzer</name></author><author><name sortKey="Holden, J E" sort="Holden, J E" uniqKey="Holden J" first="J E" last="Holden">J E Holden</name></author><author><name sortKey="Wudel, J" sort="Wudel, J" uniqKey="Wudel J" first="J" last="Wudel">J. Wudel</name></author><author><name sortKey="Pal, P K" sort="Pal, P K" uniqKey="Pal P" first="P K" last="Pal">P K Pal</name></author><author><name sortKey="De La Fuente Fernandez, R" sort="De La Fuente Fernandez, R" uniqKey="De La Fuente Fernandez R" first="R" last="De La Fuente-Fernandez">R. 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Samii</name></author><author><name sortKey="Sossi, V" sort="Sossi, V" uniqKey="Sossi V" first="V" last="Sossi">V. Sossi</name></author><author><name sortKey="Ruth, T J" sort="Ruth, T J" uniqKey="Ruth T" first="T J" last="Ruth">T J Ruth</name></author><author><name sortKey="Schulzer, M" sort="Schulzer, M" uniqKey="Schulzer M" first="M" last="Schulzer">M. Schulzer</name></author><author><name sortKey="Holden, J E" sort="Holden, J E" uniqKey="Holden J" first="J E" last="Holden">J E Holden</name></author><author><name sortKey="Wudel, J" sort="Wudel, J" uniqKey="Wudel J" first="J" last="Wudel">J. Wudel</name></author><author><name sortKey="Pal, P K" sort="Pal, P K" uniqKey="Pal P" first="P K" last="Pal">P K Pal</name></author><author><name sortKey="De La Fuente Fernandez, R" sort="De La Fuente Fernandez, R" uniqKey="De La Fuente Fernandez R" first="R" last="De La Fuente-Fernandez">R. De La Fuente-Fernandez</name></author><author><name sortKey="Calne, D B" sort="Calne, D B" uniqKey="Calne D" first="D B" last="Calne">D B Calne</name></author><author><name sortKey="Stoessl, A J" sort="Stoessl, A J" uniqKey="Stoessl A" first="A J" last="Stoessl">A J Stoessl</name></author></analytic><series><title level="j">Annals of neurology</title><idno type="ISSN">0364-5134</idno><imprint><date when="2000" type="published">2000</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged</term><term>Carbon Radioisotopes</term><term>Carrier Proteins (metabolism)</term><term>Corpus Striatum (diagnostic imaging)</term><term>Corpus Striatum (metabolism)</term><term>Dopamine (metabolism)</term><term>Dopamine Plasma Membrane Transport Proteins</term><term>Down-Regulation (physiology)</term><term>Fluorine Radioisotopes</term><term>Homovanillic Acid (metabolism)</term><term>Humans</term><term>Membrane Glycoproteins</term><term>Membrane Transport Proteins</term><term>Middle Aged</term><term>Nerve Tissue Proteins</term><term>Parkinson Disease (diagnostic imaging)</term><term>Parkinson Disease (metabolism)</term><term>Presynaptic Terminals (metabolism)</term><term>Tetrabenazine (analogs & derivatives)</term><term>Tomography, Emission-Computed</term></keywords><keywords scheme="MESH" type="chemical" qualifier="analogs & derivatives" xml:lang="en"><term>Tetrabenazine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Carrier Proteins</term><term>Dopamine</term><term>Homovanillic Acid</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Carbon Radioisotopes</term><term>Dopamine Plasma Membrane Transport Proteins</term><term>Fluorine Radioisotopes</term><term>Membrane Glycoproteins</term><term>Membrane Transport Proteins</term><term>Nerve Tissue Proteins</term></keywords><keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Corpus Striatum</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Corpus Striatum</term><term>Parkinson Disease</term><term>Presynaptic Terminals</term></keywords><keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Down-Regulation</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Aged</term><term>Humans</term><term>Middle Aged</term><term>Tomography, Emission-Computed</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Clinical symptoms of Parkinson's disease (PD) do not manifest until dopamine (DA) neuronal loss reaches a symptomatic threshold. To explore the mechanisms of functional compensation that occur in presynaptic DA nerve terminals in PD, we compared striatal positron emission tomographic (PET) measurements by using [11C]dihydrotetrabenazine ([11C]DTBZ; labeling the vesicular monoamine transporter type 2), [11C]methylphenidate (labeling the plasma membrane DA transporter), and [18F]dopa (reflecting synthesis and storage of DA). Three consecutive PET scans were performed in three-dimensional mode by using each tracer on 35 patients and 16 age-matched, normal controls. PET measurements by the three tracers were compared between subgroups of earlier and later stages of PD, between drug-naive and drug-treated subgroups of PD, and between subregions of the parkinsonian striatum. The quantitative relationships of [18F]dopa and [11]DTBZ, and of [11C]methylphenidate and [11C]DTBZ, were compared between the PD and the normal control subjects. We found that [18F]dopa Ki was reduced less than the binding potential (Bmax/Kd) for [11C]DTBZ in the parkinsonian striatum, whereas the [11C]methylphenidate binding potential was reduced more than [11C]DTBZ binding potential. These observations suggest that the activity of aromatic L-amino acid decarboxylase is up-regulated, whereas the plasma membrane DA transporter is down-regulated in the striatum of patients with PD.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Calne, D B" sort="Calne, D B" uniqKey="Calne D" first="D B" last="Calne">D B Calne</name><name sortKey="De La Fuente Fernandez, R" sort="De La Fuente Fernandez, R" uniqKey="De La Fuente Fernandez R" first="R" last="De La Fuente-Fernandez">R. De La Fuente-Fernandez</name><name sortKey="Holden, J E" sort="Holden, J E" uniqKey="Holden J" first="J E" last="Holden">J E Holden</name><name sortKey="Pal, P K" sort="Pal, P K" uniqKey="Pal P" first="P K" last="Pal">P K Pal</name><name sortKey="Ruth, T J" sort="Ruth, T J" uniqKey="Ruth T" first="T J" last="Ruth">T J Ruth</name><name sortKey="Samii, A" sort="Samii, A" uniqKey="Samii A" first="A" last="Samii">A. Samii</name><name sortKey="Schulzer, M" sort="Schulzer, M" uniqKey="Schulzer M" first="M" last="Schulzer">M. Schulzer</name><name sortKey="Sossi, V" sort="Sossi, V" uniqKey="Sossi V" first="V" last="Sossi">V. Sossi</name><name sortKey="Stoessl, A J" sort="Stoessl, A J" uniqKey="Stoessl A" first="A J" last="Stoessl">A J Stoessl</name><name sortKey="Wudel, J" sort="Wudel, J" uniqKey="Wudel J" first="J" last="Wudel">J. Wudel</name></noCountry><country name="Canada"><noRegion><name sortKey="Lee, C S" sort="Lee, C S" uniqKey="Lee C" first="C S" last="Lee">C S Lee</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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