VMAT2 binding is elevated in dopa‐responsive dystonia: Visualizing empty vesicles by PET
Identifieur interne : 002E13 ( Main/Exploration ); précédent : 002E12; suivant : 002E14VMAT2 binding is elevated in dopa‐responsive dystonia: Visualizing empty vesicles by PET
Auteurs : Raúl De La Fuente-Fernández [Canada] ; Sarah Furtado [Canada] ; Mark Guttman [Canada] ; Yoshiaki Furukawa [Canada] ; Chong S. Lee [Canada] ; Donald B. Calne [Canada] ; Thomas J. Ruth [Canada] ; A. Jon Stoessl [Canada]Source :
- Synapse [ 0887-4476 ] ; 2003-07.
English descriptors
- KwdEn :
- Adolescent, Adult, Carbon Radioisotopes, Corpus Striatum (diagnostic imaging), Corpus Striatum (metabolism), Cytoplasmic Vesicles (metabolism), Cytoplasmic Vesicles (ultrastructure), Dopamine (deficiency), Dopamine (metabolism), Dopamine Agents, Dystonic Disorders (diagnostic imaging), Dystonic Disorders (drug therapy), Dystonic Disorders (genetics), Dystonic Disorders (metabolism), Female, Fluorine Radioisotopes, Humans, Levodopa (therapeutic use), Male, Membrane Glycoproteins (metabolism), Membrane Transport Proteins, Methylphenidate, Middle Aged, Neuropeptides, Parkinson Disease (metabolism), Raclopride, Tetrabenazine (analogs & derivatives), Tomography, Emission-Computed, Vesicular Biogenic Amine Transport Proteins, Vesicular Monoamine Transport Proteins, [11C]dihydrotetrabenazine, [11C]raclopride, dopamine turnover.
- MESH :
- chemical , analogs & derivatives : Tetrabenazine.
- chemical , deficiency : Dopamine.
- chemical , metabolism : Dopamine, Membrane Glycoproteins.
- chemical , therapeutic use : Levodopa.
- chemical : Carbon Radioisotopes, Dopamine Agents, Fluorine Radioisotopes, Membrane Transport Proteins, Methylphenidate, Neuropeptides, Raclopride, Vesicular Biogenic Amine Transport Proteins, Vesicular Monoamine Transport Proteins.
- diagnostic imaging : Corpus Striatum, Dystonic Disorders.
- drug therapy : Dystonic Disorders.
- genetics : Dystonic Disorders.
- metabolism : Corpus Striatum, Cytoplasmic Vesicles, Dystonic Disorders, Parkinson Disease.
- ultrastructure : Cytoplasmic Vesicles.
- Adolescent, Adult, Female, Humans, Male, Middle Aged, Tomography, Emission-Computed.
Abstract
Dopa‐responsive dystonia (DRD) is a lifelong disorder in which dopamine deficiency is not associated with neuronal loss and therefore it is an ideal human model for investigating the compensatory changes that occur in response to this biochemical abnormality. Using positron emission tomography (PET), we examined the (±)‐α‐[11C]dihydrotetrabenazine ([11C]DTBZ) binding potential of untreated DRD patients and normal controls. Two other PET markers of presynaptic nigrostriatal function, d‐threo‐[11C]methylphenidate ([11C]MP) and 6‐[18F]fluoro‐L‐dopa ([18F]‐dopa), and [11C]raclopride were also used in the study. We found increased [11C]DTBZ binding potential in the striatum of DRD patients. By contrast, no significant changes were detected in either [11C]MP binding potential or [18F]‐dopa uptake rate constant. In addition, we found evidence for increased dopamine turnover in one DRD patient by examining changes in [11C]raclopride binding potential in relation to levodopa treatment. We propose that the increase in [11C]DTBZ binding likely reflects the dramatic decrease in the intravesicular concentration of dopamine that occurs in DRD; upregulation of vesicular monoamine transporter type 2 (VMAT2) expression may also contribute. Our findings suggest that the striatal expression of VMAT2 (as estimated by [11C]DTBZ binding) is not coregulated with dopamine synthesis. This is in keeping with a role for VMAT2 in other cellular processes (i.e., sequestration and release from the cell of potential toxic products), in addition to its importance for the quantal release of monoamines. Synapse 49:20–28, 2003. © 2003 Wiley‐Liss, Inc.
Url:
DOI: 10.1002/syn.10199
Affiliations:
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Using positron emission tomography (PET), we examined the (±)‐α‐[11C]dihydrotetrabenazine ([11C]DTBZ) binding potential of untreated DRD patients and normal controls. Two other PET markers of presynaptic nigrostriatal function, d‐threo‐[11C]methylphenidate ([11C]MP) and 6‐[18F]fluoro‐L‐dopa ([18F]‐dopa), and [11C]raclopride were also used in the study. We found increased [11C]DTBZ binding potential in the striatum of DRD patients. By contrast, no significant changes were detected in either [11C]MP binding potential or [18F]‐dopa uptake rate constant. In addition, we found evidence for increased dopamine turnover in one DRD patient by examining changes in [11C]raclopride binding potential in relation to levodopa treatment. We propose that the increase in [11C]DTBZ binding likely reflects the dramatic decrease in the intravesicular concentration of dopamine that occurs in DRD; upregulation of vesicular monoamine transporter type 2 (VMAT2) expression may also contribute. Our findings suggest that the striatal expression of VMAT2 (as estimated by [11C]DTBZ binding) is not coregulated with dopamine synthesis. This is in keeping with a role for VMAT2 in other cellular processes (i.e., sequestration and release from the cell of potential toxic products), in addition to its importance for the quantal release of monoamines. Synapse 49:20–28, 2003. © 2003 Wiley‐Liss, Inc.</div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><country name="Canada"><noRegion><name sortKey="De La Fuente Ernandez, Raul" sort="De La Fuente Ernandez, Raul" uniqKey="De La Fuente Ernandez R" first="Raúl" last="De La Fuente-Fernández">Raúl De La Fuente-Fernández</name></noRegion><name sortKey="Calne, Donald B" sort="Calne, Donald B" uniqKey="Calne D" first="Donald B." last="Calne">Donald B. Calne</name><name sortKey="Furtado, Sarah" sort="Furtado, Sarah" uniqKey="Furtado S" first="Sarah" last="Furtado">Sarah Furtado</name><name sortKey="Furukawa, Yoshiaki" sort="Furukawa, Yoshiaki" uniqKey="Furukawa Y" first="Yoshiaki" last="Furukawa">Yoshiaki Furukawa</name><name sortKey="Guttman, Mark" sort="Guttman, Mark" uniqKey="Guttman M" first="Mark" last="Guttman">Mark Guttman</name><name sortKey="Lee, Chong S" sort="Lee, Chong S" uniqKey="Lee C" first="Chong S." last="Lee">Chong S. Lee</name><name sortKey="Ruth, Thomas J" sort="Ruth, Thomas J" uniqKey="Ruth T" first="Thomas J." last="Ruth">Thomas J. Ruth</name><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A. Jon" last="Stoessl">A. Jon Stoessl</name><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A. Jon" last="Stoessl">A. Jon Stoessl</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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