Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo
Identifieur interne : 000A34 ( Main/Exploration ); précédent : 000A33; suivant : 000A35Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo
Auteurs : Kelly M. Lohr ; Alison I. Bernstein ; Kristen A. Stout ; Amy R. Dunn ; Carlos R. Lazo ; Shawn P. Alter ; Minzheng Wang ; Yingjie Li ; Xueliang Fan ; Ellen J. Hess ; Hong Yi ; Laura M. Vecchio [Canada] ; David S. Goldstein ; Thomas S. Guillot ; Ali Salahpour [Canada] ; Gary W. MillerSource :
- Proceedings of the National Academy of Sciences of the United States of America [ 0027-8424 ] ; 2014.
English descriptors
- KwdEn :
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology), Animals, Behavior, Animal, Chromosomes, Artificial, Bacterial, Corpus Striatum (metabolism), Dopamine (metabolism), Mice, Mice, Transgenic, Parkinsonian Disorders (metabolism), Parkinsonian Disorders (pathology), Parkinsonian Disorders (physiopathology), Vesicular Monoamine Transport Proteins (genetics), Vesicular Monoamine Transport Proteins (physiology).
- MESH :
- chemical , genetics : Vesicular Monoamine Transport Proteins.
- chemical , metabolism : Dopamine.
- chemical , pharmacology : 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine.
- metabolism : Corpus Striatum, Parkinsonian Disorders.
- pathology : Parkinsonian Disorders.
- chemical , physiology : Vesicular Monoamine Transport Proteins.
- physiopathology : Parkinsonian Disorders.
- Animals, Behavior, Animal, Chromosomes, Artificial, Bacterial, Mice, Mice, Transgenic.
Abstract
Several therapeutic strategies have been used to enhance monoamine neurotransmitter signaling. However, many of these interventions have deleterious side effects or lose effectiveness due to off-target actions and system feedback. These undesirable consequences likely occur because of temporal dysregulation of neurotransmitter release and uptake. We demonstrate that increasing vesicular packaging enhances dopamine neurotransmission without this signaling disruption. Mice with elevated vesicular monoamine transporter display increased dopamine release, improved outcomes on anxiety and depressive behaviors, enhanced locomotion, and protection from a Parkinson disease-related neurotoxic insult. The malleable nature of the dopamine vesicle suggests that interventions aimed at enhancing vesicle filling may be of therapeutic benefit.
Url:
DOI: 10.1073/pnas.1402134111
PubMed: 24979780
PubMed Central: 4103325
Affiliations:
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Le document en format XML
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Miller</name><affiliation><nlm:aff id="aff1">Department of Environmental Health, Rollins School of Public Health,</nlm:aff><wicri:noCountry code="subfield">Rollins School of Public Health</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Department of Pharmacology,</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Department of Neurology,</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Center for Neurodegenerative Diseases,<institution>Emory University</institution>, Atlanta,<addr-line>GA</addr-line> 30322;</nlm:aff></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">24979780</idno><idno type="pmc">4103325</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4103325</idno><idno type="RBID">PMC:4103325</idno><idno type="doi">10.1073/pnas.1402134111</idno><date when="2014">2014</date><idno type="wicri:Area/Pmc/Corpus">000672</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000672</idno><idno type="wicri:Area/Pmc/Curation">000672</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000672</idno><idno type="wicri:Area/Pmc/Checkpoint">000467</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000467</idno><idno type="wicri:source">PubMed</idno><idno type="wicri:Area/PubMed/Corpus">000719</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000719</idno><idno type="wicri:Area/PubMed/Curation">000719</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000719</idno><idno type="wicri:Area/PubMed/Checkpoint">000719</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000719</idno><idno type="wicri:Area/Ncbi/Merge">001809</idno><idno type="wicri:Area/Ncbi/Curation">001809</idno><idno type="wicri:Area/Ncbi/Checkpoint">001809</idno><idno type="wicri:doubleKey">0027-8424:2014:Lohr K:increased:vesicular:monoamine</idno><idno type="wicri:Area/Main/Merge">000A37</idno><idno type="wicri:Area/Main/Curation">000A34</idno><idno type="wicri:Area/Main/Exploration">000A34</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo</title><author><name sortKey="Lohr, Kelly M" sort="Lohr, Kelly M" uniqKey="Lohr K" first="Kelly M." last="Lohr">Kelly M. Lohr</name><affiliation><nlm:aff id="aff1">Department of Environmental Health, Rollins School of Public Health,</nlm:aff><wicri:noCountry code="subfield">Rollins School of Public Health</wicri:noCountry></affiliation></author><author><name sortKey="Bernstein, Alison I" sort="Bernstein, Alison I" uniqKey="Bernstein A" first="Alison I." last="Bernstein">Alison I. Bernstein</name><affiliation><nlm:aff id="aff1">Department of Environmental Health, Rollins School of Public Health,</nlm:aff><wicri:noCountry code="subfield">Rollins School of Public Health</wicri:noCountry></affiliation></author><author><name sortKey="Stout, Kristen A" sort="Stout, Kristen A" uniqKey="Stout K" first="Kristen A." last="Stout">Kristen A. Stout</name><affiliation><nlm:aff id="aff1">Department of Environmental Health, Rollins School of Public Health,</nlm:aff><wicri:noCountry code="subfield">Rollins School of Public Health</wicri:noCountry></affiliation></author><author><name sortKey="Dunn, Amy R" sort="Dunn, Amy R" uniqKey="Dunn A" first="Amy R." last="Dunn">Amy R. Dunn</name><affiliation><nlm:aff id="aff1">Department of Environmental Health, Rollins School of Public Health,</nlm:aff><wicri:noCountry code="subfield">Rollins School of Public Health</wicri:noCountry></affiliation></author><author><name sortKey="Lazo, Carlos R" sort="Lazo, Carlos R" uniqKey="Lazo C" first="Carlos R." last="Lazo">Carlos R. Lazo</name><affiliation><nlm:aff id="aff1">Department of Environmental Health, Rollins School of Public Health,</nlm:aff><wicri:noCountry code="subfield">Rollins School of Public Health</wicri:noCountry></affiliation></author><author><name sortKey="Alter, Shawn P" sort="Alter, Shawn P" uniqKey="Alter S" first="Shawn P." last="Alter">Shawn P. Alter</name><affiliation><nlm:aff id="aff1">Department of Environmental Health, Rollins School of Public Health,</nlm:aff><wicri:noCountry code="subfield">Rollins School of Public Health</wicri:noCountry></affiliation></author><author><name sortKey="Wang, Minzheng" sort="Wang, Minzheng" uniqKey="Wang M" first="Minzheng" last="Wang">Minzheng Wang</name><affiliation><nlm:aff id="aff1">Department of Environmental Health, Rollins School of Public Health,</nlm:aff><wicri:noCountry code="subfield">Rollins School of Public Health</wicri:noCountry></affiliation></author><author><name sortKey="Li, Yingjie" sort="Li, Yingjie" uniqKey="Li Y" first="Yingjie" last="Li">Yingjie Li</name><affiliation><nlm:aff id="aff1">Department of Environmental Health, Rollins School of Public Health,</nlm:aff><wicri:noCountry code="subfield">Rollins School of Public Health</wicri:noCountry></affiliation></author><author><name sortKey="Fan, Xueliang" sort="Fan, Xueliang" uniqKey="Fan X" first="Xueliang" last="Fan">Xueliang Fan</name><affiliation><nlm:aff id="aff3">Department of Pharmacology,</nlm:aff></affiliation></author><author><name sortKey="Hess, Ellen J" sort="Hess, Ellen J" uniqKey="Hess E" first="Ellen J." last="Hess">Ellen J. Hess</name><affiliation><nlm:aff id="aff3">Department of Pharmacology,</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Department of Neurology,</nlm:aff></affiliation></author><author><name sortKey="Yi, Hong" sort="Yi, Hong" uniqKey="Yi H" first="Hong" last="Yi">Hong Yi</name><affiliation><nlm:aff wicri:cut=", and" id="aff5">Robert P. Apkarian Integrated Electron Microscopy Core</nlm:aff></affiliation></author><author><name sortKey="Vecchio, Laura M" sort="Vecchio, Laura M" uniqKey="Vecchio L" first="Laura M." last="Vecchio">Laura M. Vecchio</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff6">Department of Pharmacology and Toxicology,<institution>University of Toronto</institution>, Toronto, ON,<country>Canada</country> M5S 1A8</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Goldstein, David S" sort="Goldstein, David S" uniqKey="Goldstein D" first="David S." last="Goldstein">David S. Goldstein</name><affiliation><nlm:aff id="aff7"><institution>National Institute of Neurological Disorders and Stroke</institution>, Bethesda,<addr-line>MD</addr-line> 20824</nlm:aff></affiliation></author><author><name sortKey="Guillot, Thomas S" sort="Guillot, Thomas S" uniqKey="Guillot T" first="Thomas S." last="Guillot">Thomas S. Guillot</name><affiliation><nlm:aff id="aff1">Department of Environmental Health, Rollins School of Public Health,</nlm:aff><wicri:noCountry code="subfield">Rollins School of Public Health</wicri:noCountry></affiliation></author><author><name sortKey="Salahpour, Ali" sort="Salahpour, Ali" uniqKey="Salahpour A" first="Ali" last="Salahpour">Ali Salahpour</name><affiliation wicri:level="1"><nlm:aff wicri:cut="; and" id="aff6">Department of Pharmacology and Toxicology,<institution>University of Toronto</institution>, Toronto, ON,<country>Canada</country> M5S 1A8</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Miller, Gary W" sort="Miller, Gary W" uniqKey="Miller G" first="Gary W." last="Miller">Gary W. Miller</name><affiliation><nlm:aff id="aff1">Department of Environmental Health, Rollins School of Public Health,</nlm:aff><wicri:noCountry code="subfield">Rollins School of Public Health</wicri:noCountry></affiliation><affiliation><nlm:aff id="aff3">Department of Pharmacology,</nlm:aff></affiliation><affiliation><nlm:aff id="aff4">Department of Neurology,</nlm:aff></affiliation><affiliation><nlm:aff id="aff2">Center for Neurodegenerative Diseases,<institution>Emory University</institution>, Atlanta,<addr-line>GA</addr-line> 30322;</nlm:aff></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="ISSN">0027-8424</idno><idno type="eISSN">1091-6490</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (pharmacology)</term><term>Animals</term><term>Behavior, Animal</term><term>Chromosomes, Artificial, Bacterial</term><term>Corpus Striatum (metabolism)</term><term>Dopamine (metabolism)</term><term>Mice</term><term>Mice, Transgenic</term><term>Parkinsonian Disorders (metabolism)</term><term>Parkinsonian Disorders (pathology)</term><term>Parkinsonian Disorders (physiopathology)</term><term>Vesicular Monoamine Transport Proteins (genetics)</term><term>Vesicular Monoamine Transport Proteins (physiology)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Vesicular Monoamine Transport Proteins</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Corpus Striatum</term><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" type="chemical" qualifier="physiology" xml:lang="en"><term>Vesicular Monoamine Transport Proteins</term></keywords><keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Parkinsonian Disorders</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Behavior, Animal</term><term>Chromosomes, Artificial, Bacterial</term><term>Mice</term><term>Mice, Transgenic</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Significance</title><p>Several therapeutic strategies have been used to enhance monoamine neurotransmitter signaling. However, many of these interventions have deleterious side effects or lose effectiveness due to off-target actions and system feedback. These undesirable consequences likely occur because of temporal dysregulation of neurotransmitter release and uptake. We demonstrate that increasing vesicular packaging enhances dopamine neurotransmission without this signaling disruption. Mice with elevated vesicular monoamine transporter display increased dopamine release, improved outcomes on anxiety and depressive behaviors, enhanced locomotion, and protection from a Parkinson disease-related neurotoxic insult. The malleable nature of the dopamine vesicle suggests that interventions aimed at enhancing vesicle filling may be of therapeutic benefit.</p></div></front></TEI><affiliations><list><country><li>Canada</li></country></list><tree><noCountry><name sortKey="Alter, Shawn P" sort="Alter, Shawn P" uniqKey="Alter S" first="Shawn P." last="Alter">Shawn P. Alter</name><name sortKey="Bernstein, Alison I" sort="Bernstein, Alison I" uniqKey="Bernstein A" first="Alison I." last="Bernstein">Alison I. Bernstein</name><name sortKey="Dunn, Amy R" sort="Dunn, Amy R" uniqKey="Dunn A" first="Amy R." last="Dunn">Amy R. Dunn</name><name sortKey="Fan, Xueliang" sort="Fan, Xueliang" uniqKey="Fan X" first="Xueliang" last="Fan">Xueliang Fan</name><name sortKey="Goldstein, David S" sort="Goldstein, David S" uniqKey="Goldstein D" first="David S." last="Goldstein">David S. Goldstein</name><name sortKey="Guillot, Thomas S" sort="Guillot, Thomas S" uniqKey="Guillot T" first="Thomas S." last="Guillot">Thomas S. Guillot</name><name sortKey="Hess, Ellen J" sort="Hess, Ellen J" uniqKey="Hess E" first="Ellen J." last="Hess">Ellen J. Hess</name><name sortKey="Lazo, Carlos R" sort="Lazo, Carlos R" uniqKey="Lazo C" first="Carlos R." last="Lazo">Carlos R. Lazo</name><name sortKey="Li, Yingjie" sort="Li, Yingjie" uniqKey="Li Y" first="Yingjie" last="Li">Yingjie Li</name><name sortKey="Lohr, Kelly M" sort="Lohr, Kelly M" uniqKey="Lohr K" first="Kelly M." last="Lohr">Kelly M. Lohr</name><name sortKey="Miller, Gary W" sort="Miller, Gary W" uniqKey="Miller G" first="Gary W." last="Miller">Gary W. Miller</name><name sortKey="Stout, Kristen A" sort="Stout, Kristen A" uniqKey="Stout K" first="Kristen A." last="Stout">Kristen A. Stout</name><name sortKey="Wang, Minzheng" sort="Wang, Minzheng" uniqKey="Wang M" first="Minzheng" last="Wang">Minzheng Wang</name><name sortKey="Yi, Hong" sort="Yi, Hong" uniqKey="Yi H" first="Hong" last="Yi">Hong Yi</name></noCountry><country name="Canada"><noRegion><name sortKey="Vecchio, Laura M" sort="Vecchio, Laura M" uniqKey="Vecchio L" first="Laura M." last="Vecchio">Laura M. Vecchio</name></noRegion><name sortKey="Salahpour, Ali" sort="Salahpour, Ali" uniqKey="Salahpour A" first="Ali" last="Salahpour">Ali Salahpour</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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