Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo.
Identifieur interne : 000719 ( PubMed/Curation ); précédent : 000718; suivant : 000720Increased 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 [États-Unis] ; Thomas S. Guillot ; Ali Salahpour [Canada] ; Gary W. Miller [États-Unis]Source :
- Proceedings of the National Academy of Sciences of the United States of America [ 1091-6490 ] ; 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
Disruption of neurotransmitter vesicle dynamics (transport, capacity, release) has been implicated in a variety of neurodegenerative and neuropsychiatric conditions. Here, we report a novel mouse model of enhanced vesicular function via bacterial artificial chromosome (BAC)-mediated overexpression of the vesicular monoamine transporter 2 (VMAT2; Slc18a2). A twofold increase in vesicular transport enhances the vesicular capacity for dopamine (56%), dopamine vesicle volume (33%), and basal tissue dopamine levels (21%) in the mouse striatum. The elevated vesicular capacity leads to an increase in stimulated dopamine release (84%) and extracellular dopamine levels (44%). VMAT2-overexpressing mice show improved outcomes on anxiety and depressive-like behaviors and increased basal locomotor activity (41%). Finally, these mice exhibit significant protection from neurotoxic insult by the dopaminergic toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as measured by reduced dopamine terminal damage and substantia nigra pars compacta cell loss. The increased release of dopamine and neuroprotection from MPTP toxicity in the VMAT2-overexpressing mice suggest that interventions aimed at enhancing vesicular capacity may be of therapeutic benefit in Parkinson disease.
DOI: 10.1073/pnas.1402134111
PubMed: 24979780
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Kelly M. Lohr<affiliation><nlm:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><wicri:noCountry code="subField">Rollins School of Public Health</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><wicri:noCountry code="subField">Rollins School of Public Health</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><wicri:noCountry code="subField">Rollins School of Public Health</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><wicri:noCountry code="subField">Rollins School of Public Health</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><wicri:noCountry code="subField">Rollins School of Public Health</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><wicri:noCountry code="subField">Rollins School of Public Health</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><wicri:noCountry code="subField">Rollins School of Public Health</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><wicri:noCountry code="subField">Rollins School of Public Health</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Department of Pharmacology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Pharmacology.</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Department of Pharmacology,Department of Neurology.</nlm:affiliation><wicri:noCountry code="subField">Department of Neurology</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Robert P. Apkarian Integrated Electron Microscopy Core, and.</nlm:affiliation><wicri:noCountry code="subField">and</wicri:noCountry></affiliation><affiliation><nlm:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><wicri:noCountry code="subField">Rollins School of Public Health</wicri:noCountry></affiliation>Le document en format XML
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Bernstein</name><affiliation><nlm:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><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:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><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. 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Hess</name><affiliation><nlm:affiliation>Department of Pharmacology,Department of Neurology.</nlm:affiliation><wicri:noCountry code="subField">Department of Neurology</wicri:noCountry></affiliation></author><author><name sortKey="Yi, Hong" sort="Yi, Hong" uniqKey="Yi H" first="Hong" last="Yi">Hong Yi</name><affiliation><nlm:affiliation>Robert P. Apkarian Integrated Electron Microscopy Core, and.</nlm:affiliation><wicri:noCountry code="subField">and</wicri:noCountry></affiliation></author><author><name sortKey="Vecchio, Laura M" sort="Vecchio, Laura M" uniqKey="Vecchio L" first="Laura M" last="Vecchio">Laura M. 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Guillot</name><affiliation><nlm:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><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:affiliation>Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada M5S 1A8; and.</nlm:affiliation><country>Canada</country><wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON</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 wicri:level="1"><nlm:affiliation>Department of Environmental Health, Rollins School of Public Health,Department of Pharmacology,Department of Neurology,Center for Neurodegenerative Diseases, Emory University, Atlanta, GA 30322; gary.miller@emory.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Department of Environmental Health, Rollins School of Public Health,Department of Pharmacology,Department of Neurology,Center for Neurodegenerative Diseases, Emory University, Atlanta</wicri:regionArea></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2014">2014</date><idno type="RBID">pubmed:24979780</idno><idno type="pmid">24979780</idno><idno type="doi">10.1073/pnas.1402134111</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></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">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:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><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:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><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:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><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:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><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:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><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:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><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:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><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:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><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:affiliation>Department of Pharmacology.</nlm:affiliation><wicri:noCountry code="no comma">Department of Pharmacology.</wicri:noCountry></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:affiliation>Department of Pharmacology,Department of Neurology.</nlm:affiliation><wicri:noCountry code="subField">Department of Neurology</wicri:noCountry></affiliation></author><author><name sortKey="Yi, Hong" sort="Yi, Hong" uniqKey="Yi H" first="Hong" last="Yi">Hong Yi</name><affiliation><nlm:affiliation>Robert P. Apkarian Integrated Electron Microscopy Core, and.</nlm:affiliation><wicri:noCountry code="subField">and</wicri:noCountry></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:affiliation>Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada M5S 1A8; and.</nlm:affiliation><country>Canada</country><wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON</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 wicri:level="2"><nlm:affiliation>National Institute of Neurological Disorders and Stroke, Bethesda, MD 20824.</nlm:affiliation><country xml:lang="fr">États-Unis</country><placeName><region type="state">Maryland</region></placeName><wicri:cityArea>National Institute of Neurological Disorders and Stroke, Bethesda</wicri:cityArea></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:affiliation>Department of Environmental Health, Rollins School of Public Health.</nlm:affiliation><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:affiliation>Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada M5S 1A8; and.</nlm:affiliation><country>Canada</country><wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON</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 wicri:level="1"><nlm:affiliation>Department of Environmental Health, Rollins School of Public Health,Department of Pharmacology,Department of Neurology,Center for Neurodegenerative Diseases, Emory University, Atlanta, GA 30322; gary.miller@emory.edu.</nlm:affiliation><country wicri:rule="url">États-Unis</country><wicri:regionArea>Department of Environmental Health, Rollins School of Public Health,Department of Pharmacology,Department of Neurology,Center for Neurodegenerative Diseases, Emory University, Atlanta</wicri:regionArea></affiliation></author></analytic><series><title level="j">Proceedings of the National Academy of Sciences of the United States of America</title><idno type="eISSN">1091-6490</idno><imprint><date when="2014" type="published">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">Disruption of neurotransmitter vesicle dynamics (transport, capacity, release) has been implicated in a variety of neurodegenerative and neuropsychiatric conditions. Here, we report a novel mouse model of enhanced vesicular function via bacterial artificial chromosome (BAC)-mediated overexpression of the vesicular monoamine transporter 2 (VMAT2; Slc18a2). A twofold increase in vesicular transport enhances the vesicular capacity for dopamine (56%), dopamine vesicle volume (33%), and basal tissue dopamine levels (21%) in the mouse striatum. The elevated vesicular capacity leads to an increase in stimulated dopamine release (84%) and extracellular dopamine levels (44%). VMAT2-overexpressing mice show improved outcomes on anxiety and depressive-like behaviors and increased basal locomotor activity (41%). Finally, these mice exhibit significant protection from neurotoxic insult by the dopaminergic toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as measured by reduced dopamine terminal damage and substantia nigra pars compacta cell loss. The increased release of dopamine and neuroprotection from MPTP toxicity in the VMAT2-overexpressing mice suggest that interventions aimed at enhancing vesicular capacity may be of therapeutic benefit in Parkinson disease.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">24979780</PMID><DateCreated><Year>2014</Year><Month>07</Month><Day>09</Day></DateCreated><DateCompleted><Year>2014</Year><Month>09</Month><Day>15</Day></DateCompleted><DateRevised><Year>2017</Year><Month>02</Month><Day>20</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">1091-6490</ISSN><JournalIssue CitedMedium="Internet"><Volume>111</Volume><Issue>27</Issue><PubDate><Year>2014</Year><Month>Jul</Month><Day>08</Day></PubDate></JournalIssue><Title>Proceedings of the National Academy of Sciences of the United States of America</Title><ISOAbbreviation>Proc. Natl. Acad. Sci. U.S.A.</ISOAbbreviation></Journal><ArticleTitle>Increased vesicular monoamine transporter enhances dopamine release and opposes Parkinson disease-related neurodegeneration in vivo.</ArticleTitle><Pagination><MedlinePgn>9977-82</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.1073/pnas.1402134111</ELocationID><Abstract><AbstractText>Disruption of neurotransmitter vesicle dynamics (transport, capacity, release) has been implicated in a variety of neurodegenerative and neuropsychiatric conditions. Here, we report a novel mouse model of enhanced vesicular function via bacterial artificial chromosome (BAC)-mediated overexpression of the vesicular monoamine transporter 2 (VMAT2; Slc18a2). A twofold increase in vesicular transport enhances the vesicular capacity for dopamine (56%), dopamine vesicle volume (33%), and basal tissue dopamine levels (21%) in the mouse striatum. The elevated vesicular capacity leads to an increase in stimulated dopamine release (84%) and extracellular dopamine levels (44%). VMAT2-overexpressing mice show improved outcomes on anxiety and depressive-like behaviors and increased basal locomotor activity (41%). Finally, these mice exhibit significant protection from neurotoxic insult by the dopaminergic toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), as measured by reduced dopamine terminal damage and substantia nigra pars compacta cell loss. The increased release of dopamine and neuroprotection from MPTP toxicity in the VMAT2-overexpressing mice suggest that interventions aimed at enhancing vesicular capacity may be of therapeutic benefit in Parkinson disease.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Lohr</LastName><ForeName>Kelly M</ForeName><Initials>KM</Initials><AffiliationInfo><Affiliation>Department of Environmental Health, Rollins School of Public Health.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bernstein</LastName><ForeName>Alison I</ForeName><Initials>AI</Initials><AffiliationInfo><Affiliation>Department of Environmental Health, Rollins School of Public Health.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stout</LastName><ForeName>Kristen A</ForeName><Initials>KA</Initials><AffiliationInfo><Affiliation>Department of Environmental Health, Rollins School of Public Health.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dunn</LastName><ForeName>Amy R</ForeName><Initials>AR</Initials><AffiliationInfo><Affiliation>Department of Environmental Health, Rollins School of Public Health.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Lazo</LastName><ForeName>Carlos R</ForeName><Initials>CR</Initials><AffiliationInfo><Affiliation>Department of Environmental Health, Rollins School of Public Health.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Alter</LastName><ForeName>Shawn P</ForeName><Initials>SP</Initials><AffiliationInfo><Affiliation>Department of Environmental Health, Rollins School of Public Health.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Wang</LastName><ForeName>Minzheng</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Department of Environmental Health, Rollins School of Public Health.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Li</LastName><ForeName>Yingjie</ForeName><Initials>Y</Initials><AffiliationInfo><Affiliation>Department of Environmental Health, Rollins School of Public Health.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Fan</LastName><ForeName>Xueliang</ForeName><Initials>X</Initials><AffiliationInfo><Affiliation>Department of Pharmacology.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hess</LastName><ForeName>Ellen J</ForeName><Initials>EJ</Initials><AffiliationInfo><Affiliation>Department of Pharmacology,Department of Neurology.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yi</LastName><ForeName>Hong</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Robert P. Apkarian Integrated Electron Microscopy Core, and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Vecchio</LastName><ForeName>Laura M</ForeName><Initials>LM</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada M5S 1A8; and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goldstein</LastName><ForeName>David S</ForeName><Initials>DS</Initials><AffiliationInfo><Affiliation>National Institute of Neurological Disorders and Stroke, Bethesda, MD 20824.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Guillot</LastName><ForeName>Thomas S</ForeName><Initials>TS</Initials><AffiliationInfo><Affiliation>Department of Environmental Health, Rollins School of Public Health.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Salahpour</LastName><ForeName>Ali</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada M5S 1A8; and.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Miller</LastName><ForeName>Gary W</ForeName><Initials>GW</Initials><AffiliationInfo><Affiliation>Department of Environmental Health, Rollins School of Public Health,Department of Pharmacology,Department of Neurology,Center for Neurodegenerative Diseases, Emory University, Atlanta, GA 30322; gary.miller@emory.edu.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>T32ES012870</GrantID><Acronym>ES</Acronym><Agency>NIEHS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30ES019776</GrantID><Acronym>ES</Acronym><Agency>NIEHS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 GM008602</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 ES012870</GrantID><Acronym>ES</Acronym><Agency>NIEHS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>210296</GrantID><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant><Grant><GrantID>P01 ES016731</GrantID><Acronym>ES</Acronym><Agency>NIEHS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P50NS071669</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32GM008605</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>F31NS084739</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 DA015040</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P01ES016731</GrantID><Acronym>ES</Acronym><Agency>NIEHS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>F31 NS084739</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P50 AG025688</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>T32 GM008605</GrantID><Acronym>GM</Acronym><Agency>NIGMS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P30 ES019776</GrantID><Acronym>ES</Acronym><Agency>NIEHS NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P50AG025688</GrantID><Acronym>AG</Acronym><Agency>NIA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>DA015040</GrantID><Acronym>DA</Acronym><Agency>NIDA NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>P50 NS071669</GrantID><Acronym>NS</Acronym><Agency>NINDS NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2014</Year><Month>06</Month><Day>16</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Proc Natl Acad Sci U S A</MedlineTA><NlmUniqueID>7505876</NlmUniqueID><ISSNLinking>0027-8424</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C493453">Slc18a2 protein, mouse</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050493">Vesicular Monoamine Transport Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>9P21XSP91P</RegistryNumber><NameOfSubstance 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