Dopamine transporter relation to dopamine turnover in Parkinson's disease: a positron emission tomography study
Objective To investigate the role of the dopamine transporter (DAT) in the regulation of synaptic dopamine (DA) levels in Parkinson's disease and its role in the preservation of DA in presynaptic terminals. Methods Ten Parkinson's disease patients (age, 62.9 ± 9.5 years; Unified Parkinson&...
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| Veröffentlicht in: | Annals of neurology 2007-11, Vol.62 (5), p.468-474 |
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| container_title | Annals of neurology |
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| creator | Sossi, Vesna de la Fuente-Fernández, Raúl Schulzer, Michael Troiano, Andre R. Ruth, Thomas J. Stoessl, A. Jon |
| description | Objective
To investigate the role of the dopamine transporter (DAT) in the regulation of synaptic dopamine (DA) levels in Parkinson's disease and its role in the preservation of DA in presynaptic terminals.
Methods
Ten Parkinson's disease patients (age, 62.9 ± 9.5 years; Unified Parkinson's Disease Rating Scale motor score in “off” state, 28.5 ± 8.2) underwent positron emission tomography with 11C‐methylphenidate (MP, a DAT marker), 11C‐dihydrotetrabenazine (a vesicular monoamine transporter 2 marker), and 18F‐fluorodopa, leading to the determination of the MP and 11C‐dihydrotetrabenazine binding potentials (BPs) and the effective distribution volume for 18F‐fluorodopa, the inverse of DA turnover. Seven patients also underwent positron emission tomography with 11C‐raclopride before and 1 hour after levodopa administration to estimate levodopa‐induced changes in synaptic DA concentration.
Results
We found a significant positive correlation between effective distribution volume and BPMP (r = 0.93; p < 0.001) and a significant negative correlation between changes in synaptic DA concentration and BPMP (r = −0.93; p = 0.04), independent of disease severity and duration.
Interpretation
These data show that in Parkinson's disease, greater DAT levels are directly associated with lower DA turnover and lower changes in synaptic DA concentration. This implies that an important functional role of DAT is to maintain relatively constant synaptic DA levels and to preserve DA in nerve terminals. A decrease in DAT, although potentially serving as a compensatory mechanism in early disease, may ultimately result in increased DA turnover and higher oscillations in synaptic DA concentration, thereby possibly predisposing toward the occurrence of motor complications as disease progresses. Ann Neurol 2007 |
| doi_str_mv | 10.1002/ana.21204 |
| format | Article |
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To investigate the role of the dopamine transporter (DAT) in the regulation of synaptic dopamine (DA) levels in Parkinson's disease and its role in the preservation of DA in presynaptic terminals.
Methods
Ten Parkinson's disease patients (age, 62.9 ± 9.5 years; Unified Parkinson's Disease Rating Scale motor score in “off” state, 28.5 ± 8.2) underwent positron emission tomography with 11C‐methylphenidate (MP, a DAT marker), 11C‐dihydrotetrabenazine (a vesicular monoamine transporter 2 marker), and 18F‐fluorodopa, leading to the determination of the MP and 11C‐dihydrotetrabenazine binding potentials (BPs) and the effective distribution volume for 18F‐fluorodopa, the inverse of DA turnover. Seven patients also underwent positron emission tomography with 11C‐raclopride before and 1 hour after levodopa administration to estimate levodopa‐induced changes in synaptic DA concentration.
Results
We found a significant positive correlation between effective distribution volume and BPMP (r = 0.93; p < 0.001) and a significant negative correlation between changes in synaptic DA concentration and BPMP (r = −0.93; p = 0.04), independent of disease severity and duration.
Interpretation
These data show that in Parkinson's disease, greater DAT levels are directly associated with lower DA turnover and lower changes in synaptic DA concentration. This implies that an important functional role of DAT is to maintain relatively constant synaptic DA levels and to preserve DA in nerve terminals. A decrease in DAT, although potentially serving as a compensatory mechanism in early disease, may ultimately result in increased DA turnover and higher oscillations in synaptic DA concentration, thereby possibly predisposing toward the occurrence of motor complications as disease progresses. Ann Neurol 2007</description><identifier>ISSN: 0364-5134</identifier><identifier>EISSN: 1531-8249</identifier><identifier>DOI: 10.1002/ana.21204</identifier><identifier>PMID: 17886297</identifier><identifier>CODEN: ANNED3</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Aged ; Biological and medical sciences ; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases ; Dopamine - metabolism ; Dopamine Plasma Membrane Transport Proteins - metabolism ; Female ; Humans ; Investigative techniques, diagnostic techniques (general aspects) ; Male ; Medical sciences ; Middle Aged ; Nervous system ; Neurology ; Parkinson Disease - diagnosis ; Parkinson Disease - metabolism ; Positron-Emission Tomography - methods ; Presynaptic Terminals - metabolism ; Protein Binding - physiology ; Radionuclide investigations</subject><ispartof>Annals of neurology, 2007-11, Vol.62 (5), p.468-474</ispartof><rights>Copyright © 2007 American Neurological Association</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4574-9ae52f48a3f966d6bffc19d3a77cde33e2b7fff7d2479cc81ea329a2c5e1274c3</citedby><cites>FETCH-LOGICAL-c4574-9ae52f48a3f966d6bffc19d3a77cde33e2b7fff7d2479cc81ea329a2c5e1274c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fana.21204$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fana.21204$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19904755$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17886297$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sossi, Vesna</creatorcontrib><creatorcontrib>de la Fuente-Fernández, Raúl</creatorcontrib><creatorcontrib>Schulzer, Michael</creatorcontrib><creatorcontrib>Troiano, Andre R.</creatorcontrib><creatorcontrib>Ruth, Thomas J.</creatorcontrib><creatorcontrib>Stoessl, A. Jon</creatorcontrib><title>Dopamine transporter relation to dopamine turnover in Parkinson's disease: a positron emission tomography study</title><title>Annals of neurology</title><addtitle>Ann Neurol</addtitle><description>Objective
To investigate the role of the dopamine transporter (DAT) in the regulation of synaptic dopamine (DA) levels in Parkinson's disease and its role in the preservation of DA in presynaptic terminals.
Methods
Ten Parkinson's disease patients (age, 62.9 ± 9.5 years; Unified Parkinson's Disease Rating Scale motor score in “off” state, 28.5 ± 8.2) underwent positron emission tomography with 11C‐methylphenidate (MP, a DAT marker), 11C‐dihydrotetrabenazine (a vesicular monoamine transporter 2 marker), and 18F‐fluorodopa, leading to the determination of the MP and 11C‐dihydrotetrabenazine binding potentials (BPs) and the effective distribution volume for 18F‐fluorodopa, the inverse of DA turnover. Seven patients also underwent positron emission tomography with 11C‐raclopride before and 1 hour after levodopa administration to estimate levodopa‐induced changes in synaptic DA concentration.
Results
We found a significant positive correlation between effective distribution volume and BPMP (r = 0.93; p < 0.001) and a significant negative correlation between changes in synaptic DA concentration and BPMP (r = −0.93; p = 0.04), independent of disease severity and duration.
Interpretation
These data show that in Parkinson's disease, greater DAT levels are directly associated with lower DA turnover and lower changes in synaptic DA concentration. This implies that an important functional role of DAT is to maintain relatively constant synaptic DA levels and to preserve DA in nerve terminals. A decrease in DAT, although potentially serving as a compensatory mechanism in early disease, may ultimately result in increased DA turnover and higher oscillations in synaptic DA concentration, thereby possibly predisposing toward the occurrence of motor complications as disease progresses. Ann Neurol 2007</description><subject>Aged</subject><subject>Biological and medical sciences</subject><subject>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</subject><subject>Dopamine - metabolism</subject><subject>Dopamine Plasma Membrane Transport Proteins - metabolism</subject><subject>Female</subject><subject>Humans</subject><subject>Investigative techniques, diagnostic techniques (general aspects)</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Nervous system</subject><subject>Neurology</subject><subject>Parkinson Disease - diagnosis</subject><subject>Parkinson Disease - metabolism</subject><subject>Positron-Emission Tomography - methods</subject><subject>Presynaptic Terminals - metabolism</subject><subject>Protein Binding - physiology</subject><subject>Radionuclide investigations</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1v1DAQhi0EokvhwB9AuQDikNZfiWNuq1IWpGWpEIijNeuMwZDEwU4K--8xZGlPnObg531n9JiQx4yeMUr5OQxwxhmn8g5ZsUqwsuFS3yUrKmpZVkzIE_IgpW-UUl0zep-cMNU0NddqRcKrMELvByymCEMaQ5wwFhE7mHwYiikU7Q0wxyFc51c_FFcQv_shheF5KlqfEBK-LKAYQ_JTzDnsfUpLQR--RBi_Hoo0ze3hIbnnoEv46DhPyafXlx8v3pTb95u3F-ttaWWlZKkBK-5kA8Lpum7rvXOW6VaAUrZFIZDvlXNOtVwqbW3DEATXwG2FjCtpxSl5tvSOMfyYMU0mX2Sx62DAMCdTa5oDSmfwxQLaGFKK6MwYfQ_xYBg1f-yabNf8tZvZJ8fSed9je0sedWbg6RGAZKFzWan16ZbTmkpVVZk7X7ifvsPD_zea9W79b3W5JHya8NdNIn-DqZVQlfm825grxtSH3buN2Yrfdgqi0Q</recordid><startdate>200711</startdate><enddate>200711</enddate><creator>Sossi, Vesna</creator><creator>de la Fuente-Fernández, Raúl</creator><creator>Schulzer, Michael</creator><creator>Troiano, Andre R.</creator><creator>Ruth, Thomas J.</creator><creator>Stoessl, A. Jon</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Willey-Liss</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>200711</creationdate><title>Dopamine transporter relation to dopamine turnover in Parkinson's disease: a positron emission tomography study</title><author>Sossi, Vesna ; de la Fuente-Fernández, Raúl ; Schulzer, Michael ; Troiano, Andre R. ; Ruth, Thomas J. ; Stoessl, A. Jon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4574-9ae52f48a3f966d6bffc19d3a77cde33e2b7fff7d2479cc81ea329a2c5e1274c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Aged</topic><topic>Biological and medical sciences</topic><topic>Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases</topic><topic>Dopamine - metabolism</topic><topic>Dopamine Plasma Membrane Transport Proteins - metabolism</topic><topic>Female</topic><topic>Humans</topic><topic>Investigative techniques, diagnostic techniques (general aspects)</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Nervous system</topic><topic>Neurology</topic><topic>Parkinson Disease - diagnosis</topic><topic>Parkinson Disease - metabolism</topic><topic>Positron-Emission Tomography - methods</topic><topic>Presynaptic Terminals - metabolism</topic><topic>Protein Binding - physiology</topic><topic>Radionuclide investigations</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sossi, Vesna</creatorcontrib><creatorcontrib>de la Fuente-Fernández, Raúl</creatorcontrib><creatorcontrib>Schulzer, Michael</creatorcontrib><creatorcontrib>Troiano, Andre R.</creatorcontrib><creatorcontrib>Ruth, Thomas J.</creatorcontrib><creatorcontrib>Stoessl, A. Jon</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Annals of neurology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sossi, Vesna</au><au>de la Fuente-Fernández, Raúl</au><au>Schulzer, Michael</au><au>Troiano, Andre R.</au><au>Ruth, Thomas J.</au><au>Stoessl, A. Jon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Dopamine transporter relation to dopamine turnover in Parkinson's disease: a positron emission tomography study</atitle><jtitle>Annals of neurology</jtitle><addtitle>Ann Neurol</addtitle><date>2007-11</date><risdate>2007</risdate><volume>62</volume><issue>5</issue><spage>468</spage><epage>474</epage><pages>468-474</pages><issn>0364-5134</issn><eissn>1531-8249</eissn><coden>ANNED3</coden><abstract>Objective
To investigate the role of the dopamine transporter (DAT) in the regulation of synaptic dopamine (DA) levels in Parkinson's disease and its role in the preservation of DA in presynaptic terminals.
Methods
Ten Parkinson's disease patients (age, 62.9 ± 9.5 years; Unified Parkinson's Disease Rating Scale motor score in “off” state, 28.5 ± 8.2) underwent positron emission tomography with 11C‐methylphenidate (MP, a DAT marker), 11C‐dihydrotetrabenazine (a vesicular monoamine transporter 2 marker), and 18F‐fluorodopa, leading to the determination of the MP and 11C‐dihydrotetrabenazine binding potentials (BPs) and the effective distribution volume for 18F‐fluorodopa, the inverse of DA turnover. Seven patients also underwent positron emission tomography with 11C‐raclopride before and 1 hour after levodopa administration to estimate levodopa‐induced changes in synaptic DA concentration.
Results
We found a significant positive correlation between effective distribution volume and BPMP (r = 0.93; p < 0.001) and a significant negative correlation between changes in synaptic DA concentration and BPMP (r = −0.93; p = 0.04), independent of disease severity and duration.
Interpretation
These data show that in Parkinson's disease, greater DAT levels are directly associated with lower DA turnover and lower changes in synaptic DA concentration. This implies that an important functional role of DAT is to maintain relatively constant synaptic DA levels and to preserve DA in nerve terminals. A decrease in DAT, although potentially serving as a compensatory mechanism in early disease, may ultimately result in increased DA turnover and higher oscillations in synaptic DA concentration, thereby possibly predisposing toward the occurrence of motor complications as disease progresses. Ann Neurol 2007</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>17886297</pmid><doi>10.1002/ana.21204</doi><tpages>7</tpages></addata></record> |
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| ispartof | Annals of neurology, 2007-11, Vol.62 (5), p.468-474 |
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| subjects | Aged Biological and medical sciences Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases Dopamine - metabolism Dopamine Plasma Membrane Transport Proteins - metabolism Female Humans Investigative techniques, diagnostic techniques (general aspects) Male Medical sciences Middle Aged Nervous system Neurology Parkinson Disease - diagnosis Parkinson Disease - metabolism Positron-Emission Tomography - methods Presynaptic Terminals - metabolism Protein Binding - physiology Radionuclide investigations |
| title | Dopamine transporter relation to dopamine turnover in Parkinson's disease: a positron emission tomography study |
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