ParkinsonCanadaV1, Main, Exploration, bibRecord, 000A35

Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and L-DOPA reversible motor deficits

Identifieur interne : 000A35 ( Main/Exploration ); précédent : 000A34; suivant : 000A36

Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and L-DOPA reversible motor deficits

Auteurs : St Masoud [Canada] ; Lm Vecchio [Canada] ; Y. Bergeron ; Mm Hossain [États-Unis] ; Lt Nguyen [Canada] ; Mk Bermejo [Canada] ; B. Kile [États-Unis] ; Td Sotnikova [Italie, Russie] ; Wb Siesser [États-Unis] ; Rr Gainetdinov [Italie, Russie] ; Rm Wightman [États-Unis] ; Mg Caron [États-Unis] ; Jr Richardson [États-Unis] ; Gw Miller [États-Unis] ; Aj Ramsey [Canada] ; M. Cyr ; A. Salahpour [Canada]

Source :

Neurobiology of disease [ 0969-9961 ] ; 2014.

RBID : PMC:4505366

English descriptors

KwdEn :
- 3,4-Dihydroxyphenylacetic Acid (metabolism), Animals, Anti-Dyskinesia Agents (pharmacology), Cell Death (physiology), Cytosol (drug effects), Cytosol (metabolism), Dopamine (metabolism), Dopamine Plasma Membrane Transport Proteins (genetics), Dopamine Plasma Membrane Transport Proteins (metabolism), Dopaminergic Neurons (drug effects), Dopaminergic Neurons (pathology), Dopaminergic Neurons (physiology), Levodopa (pharmacology), Mesencephalon (drug effects), Mesencephalon (pathology), Mesencephalon (physiopathology), Mice, Inbred C57BL, Mice, Transgenic, Motor Skills (drug effects), Motor Skills (physiology), Movement Disorders (drug therapy), Movement Disorders (pathology), Movement Disorders (physiopathology), Oxidative Stress (physiology), Parkinsonian Disorders (physiopathology), Vesicular Monoamine Transport Proteins (metabolism).
MESH :
- chemical , genetics : Dopamine Plasma Membrane Transport Proteins.
- chemical , metabolism : 3,4-Dihydroxyphenylacetic Acid, Dopamine, Dopamine Plasma Membrane Transport Proteins, Vesicular Monoamine Transport Proteins.
- chemical , pharmacology : Anti-Dyskinesia Agents, Levodopa.
- drug effects : Cytosol, Dopaminergic Neurons, Mesencephalon, Motor Skills.
- drug therapy : Movement Disorders.
- metabolism : Cytosol.
- pathology : Dopaminergic Neurons, Mesencephalon, Movement Disorders.
- physiology : Cell Death, Dopaminergic Neurons, Motor Skills, Oxidative Stress.
- physiopathology : Mesencephalon, Movement Disorders, Parkinsonian Disorders.
- Animals, Mice, Inbred C57BL, Mice, Transgenic.

Abstract

The dopamine transporter is a key protein responsible for regulating dopamine homeostasis. Its function is to transport dopamine from the extracellular space into the presynaptic neuron. Studies have suggested that accumulation of dopamine in the cytosol can trigger oxidative stress and neurotoxicity. Previously, ectopic expression of the dopamine transporter was shown to cause damage in non-dopaminergic neurons due to their inability to handle cytosolic dopamine. However, it is unknown whether increasing dopamine transporter activity will be detrimental to dopamine neurons that are inherently capable of storing and degrading dopamine. To address this issue, we characterized transgenic mice that over-express the dopamine transporter selectively in dopamine neurons. We report that dopamine transporter over-expressing (DAT-tg) mice display spontaneous loss of midbrain dopamine neurons that is accompanied by increases in oxidative stress markers, 5-S-cysteinyl-dopamine and 5-S-cysteinyl-DOPAC. In addition, metabolite-to-dopamine ratios are increased and VMAT2 protein expression is decreased in the striatum of these animals. Furthermore, DAT-tg mice also show fine motor deficits on challenging beam traversal that are reversed with L-DOPA treatment. Collectively, our findings demonstrate that even in neurons that routinely handle dopamine, increased uptake of this neurotransmitter through the dopamine transporter results in oxidative damage, neuronal loss and LDOPA reversible motor deficits. In addition, DAT over-expressing animals are highly sensitive to MPTP-induced neurotoxicity. The effects of increased dopamine uptake in these transgenic mice could shed light on the unique vulnerability of dopamine neurons in Parkinson’s disease.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505366

DOI: 10.1016/j.nbd.2014.10.016
PubMed: 25447236
PubMed Central: 4505366

Affiliations:

Le document en format XML

<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en">Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and L-DOPA reversible motor deficits</title>
<author><name sortKey="Masoud, St" sort="Masoud, St" uniqKey="Masoud S" first="St" last="Masoud">St Masoud</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vecchio, Lm" sort="Vecchio, Lm" uniqKey="Vecchio L" first="Lm" last="Vecchio">Lm Vecchio</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bergeron, Y" sort="Bergeron, Y" uniqKey="Bergeron Y" first="Y" last="Bergeron">Y. Bergeron</name>
<affiliation><nlm:aff id="A2">Department of Medical Biology, Université du Québec à Trois-Rivières, QC G9A 5H7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC G9A 5H7 Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Hossain, Mm" sort="Hossain, Mm" uniqKey="Hossain M" first="Mm" last="Hossain">Mm Hossain</name>
<affiliation wicri:level="1"><nlm:aff id="A3">Environmental and Occupational Health Sciences Institute, Rutgers, 170 Frelinghuysen Road, EOHSI 340, Piscataway, NJ 08854, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Environmental and Occupational Health Sciences Institute, Rutgers, 170 Frelinghuysen Road, EOHSI 340, Piscataway, NJ 08854</wicri:regionArea>
<wicri:noRegion>NJ 08854</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nguyen, Lt" sort="Nguyen, Lt" uniqKey="Nguyen L" first="Lt" last="Nguyen">Lt Nguyen</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bermejo, Mk" sort="Bermejo, Mk" uniqKey="Bermejo M" first="Mk" last="Bermejo">Mk Bermejo</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kile, B" sort="Kile, B" uniqKey="Kile B" first="B" last="Kile">B. Kile</name>
<affiliation wicri:level="4"><nlm:aff id="A4">Department of Chemistry, University of North Carolina at Chapel Hill, NC 27599, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry, University of North Carolina at Chapel Hill, NC 27599</wicri:regionArea>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
<placeName><settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
<region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sotnikova, Td" sort="Sotnikova, Td" uniqKey="Sotnikova T" first="Td" last="Sotnikova">Td Sotnikova</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Neuroscience and Brain Technologies, Italian Institute of Technology, Via Morego 30, Genova 16163, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Neuroscience and Brain Technologies, Italian Institute of Technology, Via Morego 30, Genova 16163</wicri:regionArea>
<wicri:noRegion>Genova 16163</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A6">Faculty of Biology and Soil Science, St. Petersburg State University, St. Petersburg 199034, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Faculty of Biology and Soil Science, St. Petersburg State University, St. Petersburg 199034</wicri:regionArea>
<wicri:noRegion>St. Petersburg 199034</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Siesser, Wb" sort="Siesser, Wb" uniqKey="Siesser W" first="Wb" last="Siesser">Wb Siesser</name>
<affiliation wicri:level="1"><nlm:aff id="A7">Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Cell Biology, Duke University Medical Center, Durham, NC 27710</wicri:regionArea>
<wicri:noRegion>NC 27710</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gainetdinov, Rr" sort="Gainetdinov, Rr" uniqKey="Gainetdinov R" first="Rr" last="Gainetdinov">Rr Gainetdinov</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Neuroscience and Brain Technologies, Italian Institute of Technology, Via Morego 30, Genova 16163, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Neuroscience and Brain Technologies, Italian Institute of Technology, Via Morego 30, Genova 16163</wicri:regionArea>
<wicri:noRegion>Genova 16163</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A6">Faculty of Biology and Soil Science, St. Petersburg State University, St. Petersburg 199034, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Faculty of Biology and Soil Science, St. Petersburg State University, St. Petersburg 199034</wicri:regionArea>
<wicri:noRegion>St. Petersburg 199034</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A8">Skolkovo Institute of Science and Technology, Skolkovo, 143025, Moscow Region, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Skolkovo Institute of Science and Technology, Skolkovo, 143025, Moscow Region</wicri:regionArea>
<wicri:noRegion>Moscow Region</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wightman, Rm" sort="Wightman, Rm" uniqKey="Wightman R" first="Rm" last="Wightman">Rm Wightman</name>
<affiliation wicri:level="4"><nlm:aff id="A4">Department of Chemistry, University of North Carolina at Chapel Hill, NC 27599, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry, University of North Carolina at Chapel Hill, NC 27599</wicri:regionArea>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
<placeName><settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
<region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Caron, Mg" sort="Caron, Mg" uniqKey="Caron M" first="Mg" last="Caron">Mg Caron</name>
<affiliation wicri:level="1"><nlm:aff id="A7">Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Cell Biology, Duke University Medical Center, Durham, NC 27710</wicri:regionArea>
<wicri:noRegion>NC 27710</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Richardson, Jr" sort="Richardson, Jr" uniqKey="Richardson J" first="Jr" last="Richardson">Jr Richardson</name>
<affiliation wicri:level="1"><nlm:aff id="A3">Environmental and Occupational Health Sciences Institute, Rutgers, 170 Frelinghuysen Road, EOHSI 340, Piscataway, NJ 08854, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Environmental and Occupational Health Sciences Institute, Rutgers, 170 Frelinghuysen Road, EOHSI 340, Piscataway, NJ 08854</wicri:regionArea>
<wicri:noRegion>NJ 08854</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Miller, Gw" sort="Miller, Gw" uniqKey="Miller G" first="Gw" last="Miller">Gw Miller</name>
<affiliation wicri:level="1"><nlm:aff id="A9">Departments of Neurology, Pharmacology and Environmental Health, Emory University, Atlanta, GA 30322, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Neurology, Pharmacology and Environmental Health, Emory University, Atlanta, GA 30322</wicri:regionArea>
<wicri:noRegion>GA 30322</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ramsey, Aj" sort="Ramsey, Aj" uniqKey="Ramsey A" first="Aj" last="Ramsey">Aj Ramsey</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cyr, M" sort="Cyr, M" uniqKey="Cyr M" first="M" last="Cyr">M. Cyr</name>
<affiliation><nlm:aff id="A2">Department of Medical Biology, Université du Québec à Trois-Rivières, QC G9A 5H7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC G9A 5H7 Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Salahpour, A" sort="Salahpour, A" uniqKey="Salahpour A" first="A" last="Salahpour">A. Salahpour</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
</titleStmt>
<publicationStmt><idno type="wicri:source">PMC</idno>
<idno type="pmid">25447236</idno>
<idno type="pmc">4505366</idno>
<idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4505366</idno>
<idno type="RBID">PMC:4505366</idno>
<idno type="doi">10.1016/j.nbd.2014.10.016</idno>
<date when="2014">2014</date>
<idno type="wicri:Area/Pmc/Corpus">000882</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000882</idno>
<idno type="wicri:Area/Pmc/Curation">000882</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000882</idno>
<idno type="wicri:Area/Pmc/Checkpoint">000468</idno>
<idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000468</idno>
<idno type="wicri:source">PubMed</idno>
<idno type="wicri:Area/PubMed/Corpus">000582</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000582</idno>
<idno type="wicri:Area/PubMed/Curation">000582</idno>
<idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000582</idno>
<idno type="wicri:Area/PubMed/Checkpoint">000582</idno>
<idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000582</idno>
<idno type="wicri:Area/Ncbi/Merge">001981</idno>
<idno type="wicri:Area/Ncbi/Curation">001981</idno>
<idno type="wicri:Area/Ncbi/Checkpoint">001981</idno>
<idno type="wicri:doubleKey">0969-9961:2014:Masoud S:increased:expression:of</idno>
<idno type="wicri:Area/Main/Merge">000A38</idno>
<idno type="wicri:Area/Main/Curation">000A35</idno>
<idno type="wicri:Area/Main/Exploration">000A35</idno>
</publicationStmt>
<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and L-DOPA reversible motor deficits</title>
<author><name sortKey="Masoud, St" sort="Masoud, St" uniqKey="Masoud S" first="St" last="Masoud">St Masoud</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Vecchio, Lm" sort="Vecchio, Lm" uniqKey="Vecchio L" first="Lm" last="Vecchio">Lm Vecchio</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bergeron, Y" sort="Bergeron, Y" uniqKey="Bergeron Y" first="Y" last="Bergeron">Y. Bergeron</name>
<affiliation><nlm:aff id="A2">Department of Medical Biology, Université du Québec à Trois-Rivières, QC G9A 5H7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC G9A 5H7 Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Hossain, Mm" sort="Hossain, Mm" uniqKey="Hossain M" first="Mm" last="Hossain">Mm Hossain</name>
<affiliation wicri:level="1"><nlm:aff id="A3">Environmental and Occupational Health Sciences Institute, Rutgers, 170 Frelinghuysen Road, EOHSI 340, Piscataway, NJ 08854, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Environmental and Occupational Health Sciences Institute, Rutgers, 170 Frelinghuysen Road, EOHSI 340, Piscataway, NJ 08854</wicri:regionArea>
<wicri:noRegion>NJ 08854</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Nguyen, Lt" sort="Nguyen, Lt" uniqKey="Nguyen L" first="Lt" last="Nguyen">Lt Nguyen</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Bermejo, Mk" sort="Bermejo, Mk" uniqKey="Bermejo M" first="Mk" last="Bermejo">Mk Bermejo</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Kile, B" sort="Kile, B" uniqKey="Kile B" first="B" last="Kile">B. Kile</name>
<affiliation wicri:level="4"><nlm:aff id="A4">Department of Chemistry, University of North Carolina at Chapel Hill, NC 27599, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry, University of North Carolina at Chapel Hill, NC 27599</wicri:regionArea>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
<placeName><settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
<region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Sotnikova, Td" sort="Sotnikova, Td" uniqKey="Sotnikova T" first="Td" last="Sotnikova">Td Sotnikova</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Neuroscience and Brain Technologies, Italian Institute of Technology, Via Morego 30, Genova 16163, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Neuroscience and Brain Technologies, Italian Institute of Technology, Via Morego 30, Genova 16163</wicri:regionArea>
<wicri:noRegion>Genova 16163</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A6">Faculty of Biology and Soil Science, St. Petersburg State University, St. Petersburg 199034, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Faculty of Biology and Soil Science, St. Petersburg State University, St. Petersburg 199034</wicri:regionArea>
<wicri:noRegion>St. Petersburg 199034</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Siesser, Wb" sort="Siesser, Wb" uniqKey="Siesser W" first="Wb" last="Siesser">Wb Siesser</name>
<affiliation wicri:level="1"><nlm:aff id="A7">Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Cell Biology, Duke University Medical Center, Durham, NC 27710</wicri:regionArea>
<wicri:noRegion>NC 27710</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Gainetdinov, Rr" sort="Gainetdinov, Rr" uniqKey="Gainetdinov R" first="Rr" last="Gainetdinov">Rr Gainetdinov</name>
<affiliation wicri:level="1"><nlm:aff id="A5">Neuroscience and Brain Technologies, Italian Institute of Technology, Via Morego 30, Genova 16163, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Neuroscience and Brain Technologies, Italian Institute of Technology, Via Morego 30, Genova 16163</wicri:regionArea>
<wicri:noRegion>Genova 16163</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A6">Faculty of Biology and Soil Science, St. Petersburg State University, St. Petersburg 199034, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Faculty of Biology and Soil Science, St. Petersburg State University, St. Petersburg 199034</wicri:regionArea>
<wicri:noRegion>St. Petersburg 199034</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="A8">Skolkovo Institute of Science and Technology, Skolkovo, 143025, Moscow Region, Russia</nlm:aff>
<country xml:lang="fr">Russie</country>
<wicri:regionArea>Skolkovo Institute of Science and Technology, Skolkovo, 143025, Moscow Region</wicri:regionArea>
<wicri:noRegion>Moscow Region</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Wightman, Rm" sort="Wightman, Rm" uniqKey="Wightman R" first="Rm" last="Wightman">Rm Wightman</name>
<affiliation wicri:level="4"><nlm:aff id="A4">Department of Chemistry, University of North Carolina at Chapel Hill, NC 27599, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Chemistry, University of North Carolina at Chapel Hill, NC 27599</wicri:regionArea>
<orgName type="university">Université de Caroline du Nord à Chapel Hill</orgName>
<placeName><settlement type="city">Chapel Hill (Caroline du Nord)</settlement>
<region type="state">Caroline du Nord</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Caron, Mg" sort="Caron, Mg" uniqKey="Caron M" first="Mg" last="Caron">Mg Caron</name>
<affiliation wicri:level="1"><nlm:aff id="A7">Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Department of Cell Biology, Duke University Medical Center, Durham, NC 27710</wicri:regionArea>
<wicri:noRegion>NC 27710</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Richardson, Jr" sort="Richardson, Jr" uniqKey="Richardson J" first="Jr" last="Richardson">Jr Richardson</name>
<affiliation wicri:level="1"><nlm:aff id="A3">Environmental and Occupational Health Sciences Institute, Rutgers, 170 Frelinghuysen Road, EOHSI 340, Piscataway, NJ 08854, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Environmental and Occupational Health Sciences Institute, Rutgers, 170 Frelinghuysen Road, EOHSI 340, Piscataway, NJ 08854</wicri:regionArea>
<wicri:noRegion>NJ 08854</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Miller, Gw" sort="Miller, Gw" uniqKey="Miller G" first="Gw" last="Miller">Gw Miller</name>
<affiliation wicri:level="1"><nlm:aff id="A9">Departments of Neurology, Pharmacology and Environmental Health, Emory University, Atlanta, GA 30322, USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<wicri:regionArea>Departments of Neurology, Pharmacology and Environmental Health, Emory University, Atlanta, GA 30322</wicri:regionArea>
<wicri:noRegion>GA 30322</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Ramsey, Aj" sort="Ramsey, Aj" uniqKey="Ramsey A" first="Aj" last="Ramsey">Aj Ramsey</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cyr, M" sort="Cyr, M" uniqKey="Cyr M" first="M" last="Cyr">M. Cyr</name>
<affiliation><nlm:aff id="A2">Department of Medical Biology, Université du Québec à Trois-Rivières, QC G9A 5H7 Canada</nlm:aff>
<wicri:noCountry code="subfield">QC G9A 5H7 Canada</wicri:noCountry>
</affiliation>
</author>
<author><name sortKey="Salahpour, A" sort="Salahpour, A" uniqKey="Salahpour A" first="A" last="Salahpour">A. Salahpour</name>
<affiliation wicri:level="4"><nlm:aff id="A1">Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8, Canada</nlm:aff>
<country xml:lang="fr">Canada</country>
<wicri:regionArea>Department of Pharmacology and Toxicology, University of Toronto, 1 King’s College Circle – Rm 4302, Toronto, ON M5S 1A8</wicri:regionArea>
<orgName type="university">Université de Toronto</orgName>
<placeName><settlement type="city">Toronto</settlement>
<region type="state">Ontario</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">Neurobiology of disease</title>
<idno type="ISSN">0969-9961</idno>
<idno type="eISSN">1095-953X</idno>
<imprint><date when="2014">2014</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>3,4-Dihydroxyphenylacetic Acid (metabolism)</term>
<term>Animals</term>
<term>Anti-Dyskinesia Agents (pharmacology)</term>
<term>Cell Death (physiology)</term>
<term>Cytosol (drug effects)</term>
<term>Cytosol (metabolism)</term>
<term>Dopamine (metabolism)</term>
<term>Dopamine Plasma Membrane Transport Proteins (genetics)</term>
<term>Dopamine Plasma Membrane Transport Proteins (metabolism)</term>
<term>Dopaminergic Neurons (drug effects)</term>
<term>Dopaminergic Neurons (pathology)</term>
<term>Dopaminergic Neurons (physiology)</term>
<term>Levodopa (pharmacology)</term>
<term>Mesencephalon (drug effects)</term>
<term>Mesencephalon (pathology)</term>
<term>Mesencephalon (physiopathology)</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Transgenic</term>
<term>Motor Skills (drug effects)</term>
<term>Motor Skills (physiology)</term>
<term>Movement Disorders (drug therapy)</term>
<term>Movement Disorders (pathology)</term>
<term>Movement Disorders (physiopathology)</term>
<term>Oxidative Stress (physiology)</term>
<term>Parkinsonian Disorders (physiopathology)</term>
<term>Vesicular Monoamine Transport Proteins (metabolism)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Dopamine Plasma Membrane Transport Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>3,4-Dihydroxyphenylacetic Acid</term>
<term>Dopamine</term>
<term>Dopamine Plasma Membrane Transport Proteins</term>
<term>Vesicular Monoamine Transport Proteins</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Anti-Dyskinesia Agents</term>
<term>Levodopa</term>
</keywords>
<keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Cytosol</term>
<term>Dopaminergic Neurons</term>
<term>Mesencephalon</term>
<term>Motor Skills</term>
</keywords>
<keywords scheme="MESH" qualifier="drug therapy" xml:lang="en"><term>Movement Disorders</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Cytosol</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Dopaminergic Neurons</term>
<term>Mesencephalon</term>
<term>Movement Disorders</term>
</keywords>
<keywords scheme="MESH" qualifier="physiology" xml:lang="en"><term>Cell Death</term>
<term>Dopaminergic Neurons</term>
<term>Motor Skills</term>
<term>Oxidative Stress</term>
</keywords>
<keywords scheme="MESH" qualifier="physiopathology" xml:lang="en"><term>Mesencephalon</term>
<term>Movement Disorders</term>
<term>Parkinsonian Disorders</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Mice, Inbred C57BL</term>
<term>Mice, Transgenic</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en"><p id="P17">The dopamine transporter is a key protein responsible for regulating dopamine homeostasis. Its function is to transport dopamine from the extracellular space into the presynaptic neuron. Studies have suggested that accumulation of dopamine in the cytosol can trigger oxidative stress and neurotoxicity. Previously, ectopic expression of the dopamine transporter was shown to cause damage in non-dopaminergic neurons due to their inability to handle cytosolic dopamine. However, it is unknown whether increasing dopamine transporter activity will be detrimental to dopamine neurons that are inherently capable of storing and degrading dopamine. To address this issue, we characterized transgenic mice that over-express the dopamine transporter selectively in dopamine neurons. We report that dopamine transporter over-expressing (DAT-tg) mice display spontaneous loss of midbrain dopamine neurons that is accompanied by increases in oxidative stress markers, 5-S-cysteinyl-dopamine and 5-S-cysteinyl-DOPAC. In addition, metabolite-to-dopamine ratios are increased and VMAT2 protein expression is decreased in the striatum of these animals. Furthermore, DAT-tg mice also show fine motor deficits on challenging beam traversal that are reversed with L-DOPA treatment. Collectively, our findings demonstrate that even in neurons that routinely handle dopamine, increased uptake of this neurotransmitter through the dopamine transporter results in oxidative damage, neuronal loss and LDOPA reversible motor deficits. In addition, DAT over-expressing animals are highly sensitive to MPTP-induced neurotoxicity. The effects of increased dopamine uptake in these transgenic mice could shed light on the unique vulnerability of dopamine neurons in Parkinson’s disease.</p>
</div>
</front>
</TEI>
<affiliations><list><country><li>Canada</li>
<li>Italie</li>
<li>Russie</li>
<li>États-Unis</li>
</country>
<region><li>Caroline du Nord</li>
<li>Ontario</li>
</region>
<settlement><li>Chapel Hill (Caroline du Nord)</li>
<li>Toronto</li>
</settlement>
<orgName><li>Université de Caroline du Nord à Chapel Hill</li>
<li>Université de Toronto</li>
</orgName>
</list>
<tree><noCountry><name sortKey="Bergeron, Y" sort="Bergeron, Y" uniqKey="Bergeron Y" first="Y" last="Bergeron">Y. Bergeron</name>
<name sortKey="Cyr, M" sort="Cyr, M" uniqKey="Cyr M" first="M" last="Cyr">M. Cyr</name>
</noCountry>
<country name="Canada"><region name="Ontario"><name sortKey="Masoud, St" sort="Masoud, St" uniqKey="Masoud S" first="St" last="Masoud">St Masoud</name>
</region>
<name sortKey="Bermejo, Mk" sort="Bermejo, Mk" uniqKey="Bermejo M" first="Mk" last="Bermejo">Mk Bermejo</name>
<name sortKey="Nguyen, Lt" sort="Nguyen, Lt" uniqKey="Nguyen L" first="Lt" last="Nguyen">Lt Nguyen</name>
<name sortKey="Ramsey, Aj" sort="Ramsey, Aj" uniqKey="Ramsey A" first="Aj" last="Ramsey">Aj Ramsey</name>
<name sortKey="Salahpour, A" sort="Salahpour, A" uniqKey="Salahpour A" first="A" last="Salahpour">A. Salahpour</name>
<name sortKey="Vecchio, Lm" sort="Vecchio, Lm" uniqKey="Vecchio L" first="Lm" last="Vecchio">Lm Vecchio</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Hossain, Mm" sort="Hossain, Mm" uniqKey="Hossain M" first="Mm" last="Hossain">Mm Hossain</name>
</noRegion>
<name sortKey="Caron, Mg" sort="Caron, Mg" uniqKey="Caron M" first="Mg" last="Caron">Mg Caron</name>
<name sortKey="Kile, B" sort="Kile, B" uniqKey="Kile B" first="B" last="Kile">B. Kile</name>
<name sortKey="Miller, Gw" sort="Miller, Gw" uniqKey="Miller G" first="Gw" last="Miller">Gw Miller</name>
<name sortKey="Richardson, Jr" sort="Richardson, Jr" uniqKey="Richardson J" first="Jr" last="Richardson">Jr Richardson</name>
<name sortKey="Siesser, Wb" sort="Siesser, Wb" uniqKey="Siesser W" first="Wb" last="Siesser">Wb Siesser</name>
<name sortKey="Wightman, Rm" sort="Wightman, Rm" uniqKey="Wightman R" first="Rm" last="Wightman">Rm Wightman</name>
</country>
<country name="Italie"><noRegion><name sortKey="Sotnikova, Td" sort="Sotnikova, Td" uniqKey="Sotnikova T" first="Td" last="Sotnikova">Td Sotnikova</name>
</noRegion>
<name sortKey="Gainetdinov, Rr" sort="Gainetdinov, Rr" uniqKey="Gainetdinov R" first="Rr" last="Gainetdinov">Rr Gainetdinov</name>
</country>
<country name="Russie"><noRegion><name sortKey="Sotnikova, Td" sort="Sotnikova, Td" uniqKey="Sotnikova T" first="Td" last="Sotnikova">Td Sotnikova</name>
</noRegion>
<name sortKey="Gainetdinov, Rr" sort="Gainetdinov, Rr" uniqKey="Gainetdinov R" first="Rr" last="Gainetdinov">Rr Gainetdinov</name>
<name sortKey="Gainetdinov, Rr" sort="Gainetdinov, Rr" uniqKey="Gainetdinov R" first="Rr" last="Gainetdinov">Rr Gainetdinov</name>
</country>
</tree>
</affiliations>
</record>

Pour manipuler ce document sous Unix (Dilib)

EXPLOR_STEP=$WICRI_ROOT/Wicri/Canada/explor/ParkinsonCanadaV1/Data/Main/Exploration

HfdSelect -h $EXPLOR_STEP/biblio.hfd -nk 000A35 | SxmlIndent | more

HfdSelect -h $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd -nk 000A35 | SxmlIndent | more

Pour mettre un lien sur cette page dans le réseau Wicri

{{Explor lien
   |wiki=    Wicri/Canada
   |area=    ParkinsonCanadaV1
   |flux=    Main
   |étape=   Exploration
   |type=    RBID
   |clé=     PMC:4505366
   |texte=   Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and L-DOPA reversible motor deficits
}}

Pour générer des pages wiki

HfdIndexSelect -h $EXPLOR_AREA/Data/Main/Exploration/RBID.i   -Sk "pubmed:25447236" \
       | HfdSelect -Kh $EXPLOR_AREA/Data/Main/Exploration/biblio.hfd   \
       | NlmPubMed2Wicri -a ParkinsonCanadaV1

This area was generated with Dilib version V0.6.29.
Data generation: Thu May 4 22:20:19 2017. Site generation: Fri Dec 23 23:17:26 2022

La maladie de Parkinson au Canada (serveur d'exploration)

Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and L-DOPA reversible motor deficits

Increased expression of the dopamine transporter leads to loss of dopamine neurons, oxidative stress and L-DOPA reversible motor deficits

Source :

English descriptors

Abstract

Links toward previous steps (curation, corpus...)

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

Pour mettre un lien sur cette page dans le réseau Wicri

Pour générer des pages wiki

	La maladie de Parkinson au Canada (serveur d'exploration)
	Attention, ce site est en cours de développement ! Attention, site généré par des moyens informatiques à partir de corpus bruts. Les informations ne sont donc pas validées.