Behavioral deficits and striatal DA signaling in LRRK2 p.G2019S transgenic rats: a multimodal investigation including PET neuroimaging.
Identifieur interne : 000786 ( PubMed/Checkpoint ); précédent : 000785; suivant : 000787Behavioral deficits and striatal DA signaling in LRRK2 p.G2019S transgenic rats: a multimodal investigation including PET neuroimaging.
Auteurs : Matthew D. Walker [Canada] ; Mattia Volta [Canada] ; Stefano Cataldi [Canada] ; Katherine Dinelle [Canada] ; Dayne Beccano-Kelly [Canada] ; Lise Munsie [Canada] ; Rick Kornelsen [Canada] ; Chenoa Mah [Canada] ; Patrick Chou [Canada] ; Kimberley Co [Canada] ; Jaskaran Khinda [Canada] ; Marta Mroczek [Canada] ; Sabrina Bergeron [Canada] ; Katrina Yu [Canada] ; Li Ping Cao [Canada] ; Natalja Funk [Allemagne] ; Thomas Ott [Allemagne] ; Dagmar Galter [Suède] ; Olaf Riess [Allemagne] ; Saskia Biskup [Allemagne] ; Austen J. Milnerwood [Canada] ; A Jon Stoessl [Canada] ; Matthew J. Farrer [Canada] ; Vesna Sossi [Canada]Source :
- Journal of Parkinson's disease [ 1877-718X ] ; 2014.
English descriptors
- KwdEn :
- Animals, Brain (diagnostic imaging), Brain (metabolism), Disease Models, Animal, Dopamine (metabolism), Dopamine Plasma Membrane Transport Proteins (metabolism), Dopamine and cAMP-Regulated Phosphoprotein 32 (metabolism), Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Male, Motor Activity (genetics), Neostriatum (diagnostic imaging), Neostriatum (metabolism), Parkinson Disease (genetics), Phosphorylation, Positron-Emission Tomography, Protein-Serine-Threonine Kinases (genetics), Rats, Rats, Sprague-Dawley, Rats, Transgenic, Receptors, Dopamine D2 (metabolism), Rotarod Performance Test, Tyrosine 3-Monooxygenase (metabolism), Vesicular Monoamine Transport Proteins (metabolism).
- MESH :
- chemical , genetics : Protein-Serine-Threonine Kinases.
- chemical , metabolism : Dopamine, Dopamine Plasma Membrane Transport Proteins, Dopamine and cAMP-Regulated Phosphoprotein 32, Receptors, Dopamine D2, Tyrosine 3-Monooxygenase, Vesicular Monoamine Transport Proteins.
- diagnostic imaging : Brain, Neostriatum.
- genetics : Motor Activity, Parkinson Disease.
- metabolism : Brain, Neostriatum.
- Animals, Disease Models, Animal, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Male, Phosphorylation, Positron-Emission Tomography, Rats, Rats, Sprague-Dawley, Rats, Transgenic, Rotarod Performance Test.
Abstract
A major risk-factor for developing Parkinson's disease (PD) is genetic variability in leucine-rich repeat kinase 2 (LRRK2), most notably the p.G2019S mutation. Examination of the effects of this mutation is necessary to determine the etiology of PD and to guide therapeutic development.
DOI: 10.3233/JPD-140344
PubMed: 25000966
Affiliations:
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Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases DZNE, Tübingen</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></affiliation></author><author><name sortKey="Milnerwood, Austen J" sort="Milnerwood, Austen J" uniqKey="Milnerwood A" first="Austen J" last="Milnerwood">Austen J. Milnerwood</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A Jon" last="Stoessl">A Jon Stoessl</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J" last="Farrer">Matthew J. 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Walker</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physics & Astronomy, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Volta, Mattia" sort="Volta, Mattia" uniqKey="Volta M" first="Mattia" last="Volta">Mattia Volta</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Cataldi, Stefano" sort="Cataldi, Stefano" uniqKey="Cataldi S" first="Stefano" last="Cataldi">Stefano Cataldi</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Dinelle, Katherine" sort="Dinelle, Katherine" uniqKey="Dinelle K" first="Katherine" last="Dinelle">Katherine Dinelle</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Beccano Kelly, Dayne" sort="Beccano Kelly, Dayne" uniqKey="Beccano Kelly D" first="Dayne" last="Beccano-Kelly">Dayne Beccano-Kelly</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Munsie, Lise" sort="Munsie, Lise" uniqKey="Munsie L" first="Lise" last="Munsie">Lise Munsie</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Kornelsen, Rick" sort="Kornelsen, Rick" uniqKey="Kornelsen R" first="Rick" last="Kornelsen">Rick Kornelsen</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Mah, Chenoa" sort="Mah, Chenoa" uniqKey="Mah C" first="Chenoa" last="Mah">Chenoa Mah</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Chou, Patrick" sort="Chou, Patrick" uniqKey="Chou P" first="Patrick" last="Chou">Patrick Chou</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Co, Kimberley" sort="Co, Kimberley" uniqKey="Co K" first="Kimberley" last="Co">Kimberley Co</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Khinda, Jaskaran" sort="Khinda, Jaskaran" uniqKey="Khinda J" first="Jaskaran" last="Khinda">Jaskaran Khinda</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Mroczek, Marta" sort="Mroczek, Marta" uniqKey="Mroczek M" first="Marta" last="Mroczek">Marta Mroczek</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Bergeron, Sabrina" sort="Bergeron, Sabrina" uniqKey="Bergeron S" first="Sabrina" last="Bergeron">Sabrina Bergeron</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Yu, Katrina" sort="Yu, Katrina" uniqKey="Yu K" first="Katrina" last="Yu">Katrina Yu</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Cao, Li Ping" sort="Cao, Li Ping" uniqKey="Cao L" first="Li Ping" last="Cao">Li Ping Cao</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Funk, Natalja" sort="Funk, Natalja" uniqKey="Funk N" first="Natalja" last="Funk">Natalja Funk</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases DZNE, Tübingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases DZNE, Tübingen</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></affiliation></author><author><name sortKey="Ott, Thomas" sort="Ott, Thomas" uniqKey="Ott T" first="Thomas" last="Ott">Thomas Ott</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Genetics, University of Tübingen, Tübingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medical Genetics, University of Tübingen, Tübingen</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></affiliation></author><author><name sortKey="Galter, Dagmar" sort="Galter, Dagmar" uniqKey="Galter D" first="Dagmar" last="Galter">Dagmar Galter</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.</nlm:affiliation><country xml:lang="fr">Suède</country><wicri:regionArea>Department of Neuroscience, Karolinska Institutet, Stockholm</wicri:regionArea><placeName><settlement type="city">Stockholm</settlement><region nuts="2">Svealand</region></placeName></affiliation></author><author><name sortKey="Riess, Olaf" sort="Riess, Olaf" uniqKey="Riess O" first="Olaf" last="Riess">Olaf Riess</name><affiliation wicri:level="3"><nlm:affiliation>Department of Medical Genetics, University of Tübingen, Tübingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medical Genetics, University of Tübingen, Tübingen</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></affiliation></author><author><name sortKey="Biskup, Saskia" sort="Biskup, Saskia" uniqKey="Biskup S" first="Saskia" last="Biskup">Saskia Biskup</name><affiliation wicri:level="3"><nlm:affiliation>Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases DZNE, Tübingen, Germany.</nlm:affiliation><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases DZNE, Tübingen</wicri:regionArea><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Tübingen</region><settlement type="city">Tübingen</settlement></placeName></affiliation></author><author><name sortKey="Milnerwood, Austen J" sort="Milnerwood, Austen J" uniqKey="Milnerwood A" first="Austen J" last="Milnerwood">Austen J. Milnerwood</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A Jon" last="Stoessl">A Jon Stoessl</name><affiliation wicri:level="1"><nlm:affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J" last="Farrer">Matthew J. Farrer</name><affiliation wicri:level="1"><nlm:affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author><author><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><affiliation wicri:level="1"><nlm:affiliation>Department of Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada.</nlm:affiliation><country xml:lang="fr">Canada</country><wicri:regionArea>Department of Physics & Astronomy, University of British Columbia, Vancouver, BC</wicri:regionArea><wicri:noRegion>BC</wicri:noRegion></affiliation></author></analytic><series><title level="j">Journal of Parkinson's disease</title><idno type="eISSN">1877-718X</idno><imprint><date when="2014" type="published">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Brain (diagnostic imaging)</term><term>Brain (metabolism)</term><term>Disease Models, Animal</term><term>Dopamine (metabolism)</term><term>Dopamine Plasma Membrane Transport Proteins (metabolism)</term><term>Dopamine and cAMP-Regulated Phosphoprotein 32 (metabolism)</term><term>Humans</term><term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</term><term>Male</term><term>Motor Activity (genetics)</term><term>Neostriatum (diagnostic imaging)</term><term>Neostriatum (metabolism)</term><term>Parkinson Disease (genetics)</term><term>Phosphorylation</term><term>Positron-Emission Tomography</term><term>Protein-Serine-Threonine Kinases (genetics)</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Rats, Transgenic</term><term>Receptors, Dopamine D2 (metabolism)</term><term>Rotarod Performance Test</term><term>Tyrosine 3-Monooxygenase (metabolism)</term><term>Vesicular Monoamine Transport Proteins (metabolism)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Protein-Serine-Threonine Kinases</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Dopamine</term><term>Dopamine Plasma Membrane Transport Proteins</term><term>Dopamine and cAMP-Regulated Phosphoprotein 32</term><term>Receptors, Dopamine D2</term><term>Tyrosine 3-Monooxygenase</term><term>Vesicular Monoamine Transport Proteins</term></keywords><keywords scheme="MESH" qualifier="diagnostic imaging" xml:lang="en"><term>Brain</term><term>Neostriatum</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Motor Activity</term><term>Parkinson Disease</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Brain</term><term>Neostriatum</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Disease Models, Animal</term><term>Humans</term><term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</term><term>Male</term><term>Phosphorylation</term><term>Positron-Emission Tomography</term><term>Rats</term><term>Rats, Sprague-Dawley</term><term>Rats, Transgenic</term><term>Rotarod Performance Test</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">A major risk-factor for developing Parkinson's disease (PD) is genetic variability in leucine-rich repeat kinase 2 (LRRK2), most notably the p.G2019S mutation. Examination of the effects of this mutation is necessary to determine the etiology of PD and to guide therapeutic development.</div></front></TEI><pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">25000966</PMID><DateCreated><Year>2014</Year><Month>09</Month><Day>03</Day></DateCreated><DateCompleted><Year>2015</Year><Month>07</Month><Day>27</Day></DateCompleted><DateRevised><Year>2016</Year><Month>11</Month><Day>25</Day></DateRevised><Article PubModel="Print"><Journal><ISSN IssnType="Electronic">1877-718X</ISSN><JournalIssue CitedMedium="Internet"><Volume>4</Volume><Issue>3</Issue><PubDate><Year>2014</Year></PubDate></JournalIssue><Title>Journal of Parkinson's disease</Title><ISOAbbreviation>J Parkinsons Dis</ISOAbbreviation></Journal><ArticleTitle>Behavioral deficits and striatal DA signaling in LRRK2 p.G2019S transgenic rats: a multimodal investigation including PET neuroimaging.</ArticleTitle><Pagination><MedlinePgn>483-98</MedlinePgn></Pagination><ELocationID EIdType="doi" ValidYN="Y">10.3233/JPD-140344</ELocationID><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">A major risk-factor for developing Parkinson's disease (PD) is genetic variability in leucine-rich repeat kinase 2 (LRRK2), most notably the p.G2019S mutation. Examination of the effects of this mutation is necessary to determine the etiology of PD and to guide therapeutic development.</AbstractText><AbstractText Label="OBJECTIVE" NlmCategory="OBJECTIVE">Assess the behavioral consequences of LRRK2 p.G2019S overexpression in transgenic rats as they age and test the functional integrity of the nigro-striatal dopamine system. Conduct positron emission tomography (PET) neuroimaging to compare transgenic rats with previous data from human LRRK2 mutation carriers.</AbstractText><AbstractText Label="METHODS" NlmCategory="METHODS">Rats overexpressing human LRRK2 p.G2019S were generated by BAC transgenesis and compared to non-transgenic (NT) littermates. Motor skill tests were performed at 3, 6 and 12 months-of-age. PET, performed at 12 months, assessed the density of dopamine and vesicular monoamine transporters (DAT and VMAT2, respectively) and measured dopamine synthesis, storage and availability. Brain tissue was assayed for D2, DAT, dopamine and cAMP-regulated phosphoprotein (DARPP32) and tyrosine hydroxylase (TH) expression by Western blot, and TH by immunohistochemistry.</AbstractText><AbstractText Label="RESULTS" NlmCategory="RESULTS">Transgenic rats had no abnormalities in measures of striatal dopamine function at 12 months. A behavioral phenotype was present, with LRRK2 p.G2019S rats performing significantly worse on the rotarod than non-transgenic littermates (26% reduction in average running duration at 6 months), but with normal performance in other motor tests.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Neuroimaging using dopaminergic PET did not recapitulate prior studies in human LRRK2 mutation carriers. Consistently, LRRK2 p.G2019S rats do not develop overt neurodegeneration; however, they do exhibit behavioral abnormalities.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Walker</LastName><ForeName>Matthew D</ForeName><Initials>MD</Initials><AffiliationInfo><Affiliation>Department of Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Volta</LastName><ForeName>Mattia</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cataldi</LastName><ForeName>Stefano</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Dinelle</LastName><ForeName>Katherine</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Beccano-Kelly</LastName><ForeName>Dayne</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Munsie</LastName><ForeName>Lise</ForeName><Initials>L</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kornelsen</LastName><ForeName>Rick</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mah</LastName><ForeName>Chenoa</ForeName><Initials>C</Initials><AffiliationInfo><Affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Chou</LastName><ForeName>Patrick</ForeName><Initials>P</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Co</LastName><ForeName>Kimberley</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Khinda</LastName><ForeName>Jaskaran</ForeName><Initials>J</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Mroczek</LastName><ForeName>Marta</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Bergeron</LastName><ForeName>Sabrina</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Yu</LastName><ForeName>Katrina</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cao</LastName><ForeName>Li Ping</ForeName><Initials>LP</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Funk</LastName><ForeName>Natalja</ForeName><Initials>N</Initials><AffiliationInfo><Affiliation>Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases DZNE, Tübingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ott</LastName><ForeName>Thomas</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Medical Genetics, University of Tübingen, Tübingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Galter</LastName><ForeName>Dagmar</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Riess</LastName><ForeName>Olaf</ForeName><Initials>O</Initials><AffiliationInfo><Affiliation>Department of Medical Genetics, University of Tübingen, Tübingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Biskup</LastName><ForeName>Saskia</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Neurodegeneration, Hertie Institute for Clinical Brain Research and German Center for Neurodegenerative Diseases DZNE, Tübingen, Germany.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Milnerwood</LastName><ForeName>Austen J</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Stoessl</LastName><ForeName>A Jon</ForeName><Initials>AJ</Initials><AffiliationInfo><Affiliation>Pacific Parkinson's Research Centre, University of British Columbia, Vancouver, BC, Canada Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Farrer</LastName><ForeName>Matthew J</ForeName><Initials>MJ</Initials><AffiliationInfo><Affiliation>Centre for Applied Neurogenetics, Department of Medical Genetics, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Sossi</LastName><ForeName>Vesna</ForeName><Initials>V</Initials><AffiliationInfo><Affiliation>Department of Physics & Astronomy, University of British Columbia, Vancouver, BC, Canada.</Affiliation></AffiliationInfo></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>MFE 123709</GrantID><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant><Grant><GrantID>MOP 119347</GrantID><Agency>Canadian Institutes of Health Research</Agency><Country>Canada</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType></PublicationTypeList></Article><MedlineJournalInfo><Country>Netherlands</Country><MedlineTA>J Parkinsons Dis</MedlineTA><NlmUniqueID>101567362</NlmUniqueID><ISSNLinking>1877-7171</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050483">Dopamine Plasma Membrane Transport Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D051937">Dopamine and cAMP-Regulated Phosphoprotein 32</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C497930">Ppp1r1b protein, rat</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D017448">Receptors, Dopamine D2</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="C493454">Slc18a2 protein, rat</NameOfSubstance></Chemical><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D050493">Vesicular Monoamine Transport Proteins</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 1.14.16.2</RegistryNumber><NameOfSubstance UI="D014446">Tyrosine 3-Monooxygenase</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="C495280">LRRK2 protein, human</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D000071158">Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</NameOfSubstance></Chemical><Chemical><RegistryNumber>EC 2.7.11.1</RegistryNumber><NameOfSubstance UI="D017346">Protein-Serine-Threonine Kinases</NameOfSubstance></Chemical><Chemical><RegistryNumber>VTD58H1Z2X</RegistryNumber><NameOfSubstance UI="D004298">Dopamine</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D001921" MajorTopicYN="N">Brain</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="Y">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004298" MajorTopicYN="N">Dopamine</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D050483" MajorTopicYN="N">Dopamine Plasma Membrane Transport Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051937" MajorTopicYN="N">Dopamine and cAMP-Regulated Phosphoprotein 32</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000071158" MajorTopicYN="N">Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D009043" MajorTopicYN="N">Motor Activity</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017072" MajorTopicYN="N">Neostriatum</DescriptorName><QualifierName UI="Q000000981" MajorTopicYN="N">diagnostic imaging</QualifierName><QualifierName UI="Q000378" MajorTopicYN="Y">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010300" MajorTopicYN="N">Parkinson Disease</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D010766" MajorTopicYN="N">Phosphorylation</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D049268" MajorTopicYN="N">Positron-Emission Tomography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017346" MajorTopicYN="N">Protein-Serine-Threonine Kinases</DescriptorName><QualifierName UI="Q000235" MajorTopicYN="Y">genetics</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D051381" MajorTopicYN="N">Rats</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017207" MajorTopicYN="N">Rats, Sprague-Dawley</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D055647" MajorTopicYN="N">Rats, Transgenic</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D017448" MajorTopicYN="N">Receptors, Dopamine D2</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D045442" MajorTopicYN="N">Rotarod Performance Test</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D014446" MajorTopicYN="N">Tyrosine 3-Monooxygenase</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D050493" MajorTopicYN="N">Vesicular Monoamine Transport Proteins</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading></MeshHeadingList><KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="N">LRRK2 protein</Keyword><Keyword MajorTopicYN="N">Parkinson's disease</Keyword><Keyword MajorTopicYN="N">brain imaging</Keyword><Keyword MajorTopicYN="N">dopamine</Keyword><Keyword MajorTopicYN="N">dopaminergic neurons</Keyword><Keyword MajorTopicYN="N">human</Keyword><Keyword MajorTopicYN="N">positron-emission tomography</Keyword><Keyword MajorTopicYN="N">transgenic rats</Keyword></KeywordList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2014</Year><Month>7</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="pubmed"><Year>2014</Year><Month>7</Month><Day>9</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2015</Year><Month>7</Month><Day>28</Day><Hour>6</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">25000966</ArticleId><ArticleId IdType="pii">05776434P4JT6661</ArticleId><ArticleId IdType="doi">10.3233/JPD-140344</ArticleId></ArticleIdList></PubmedData></pubmed><affiliations><list><country><li>Allemagne</li><li>Canada</li><li>Suède</li></country><region><li>Bade-Wurtemberg</li><li>District de Tübingen</li><li>Svealand</li></region><settlement><li>Stockholm</li><li>Tübingen</li></settlement></list><tree><country name="Canada"><noRegion><name sortKey="Walker, Matthew D" sort="Walker, Matthew D" uniqKey="Walker M" first="Matthew D" last="Walker">Matthew D. Walker</name></noRegion><name sortKey="Beccano Kelly, Dayne" sort="Beccano Kelly, Dayne" uniqKey="Beccano Kelly D" first="Dayne" last="Beccano-Kelly">Dayne Beccano-Kelly</name><name sortKey="Bergeron, Sabrina" sort="Bergeron, Sabrina" uniqKey="Bergeron S" first="Sabrina" last="Bergeron">Sabrina Bergeron</name><name sortKey="Cao, Li Ping" sort="Cao, Li Ping" uniqKey="Cao L" first="Li Ping" last="Cao">Li Ping Cao</name><name sortKey="Cataldi, Stefano" sort="Cataldi, Stefano" uniqKey="Cataldi S" first="Stefano" last="Cataldi">Stefano Cataldi</name><name sortKey="Chou, Patrick" sort="Chou, Patrick" uniqKey="Chou P" first="Patrick" last="Chou">Patrick Chou</name><name sortKey="Co, Kimberley" sort="Co, Kimberley" uniqKey="Co K" first="Kimberley" last="Co">Kimberley Co</name><name sortKey="Dinelle, Katherine" sort="Dinelle, Katherine" uniqKey="Dinelle K" first="Katherine" last="Dinelle">Katherine Dinelle</name><name sortKey="Farrer, Matthew J" sort="Farrer, Matthew J" uniqKey="Farrer M" first="Matthew J" last="Farrer">Matthew J. Farrer</name><name sortKey="Khinda, Jaskaran" sort="Khinda, Jaskaran" uniqKey="Khinda J" first="Jaskaran" last="Khinda">Jaskaran Khinda</name><name sortKey="Kornelsen, Rick" sort="Kornelsen, Rick" uniqKey="Kornelsen R" first="Rick" last="Kornelsen">Rick Kornelsen</name><name sortKey="Mah, Chenoa" sort="Mah, Chenoa" uniqKey="Mah C" first="Chenoa" last="Mah">Chenoa Mah</name><name sortKey="Milnerwood, Austen J" sort="Milnerwood, Austen J" uniqKey="Milnerwood A" first="Austen J" last="Milnerwood">Austen J. Milnerwood</name><name sortKey="Mroczek, Marta" sort="Mroczek, Marta" uniqKey="Mroczek M" first="Marta" last="Mroczek">Marta Mroczek</name><name sortKey="Munsie, Lise" sort="Munsie, Lise" uniqKey="Munsie L" first="Lise" last="Munsie">Lise Munsie</name><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name><name sortKey="Stoessl, A Jon" sort="Stoessl, A Jon" uniqKey="Stoessl A" first="A Jon" last="Stoessl">A Jon Stoessl</name><name sortKey="Volta, Mattia" sort="Volta, Mattia" uniqKey="Volta M" first="Mattia" last="Volta">Mattia Volta</name><name sortKey="Yu, Katrina" sort="Yu, Katrina" uniqKey="Yu K" first="Katrina" last="Yu">Katrina Yu</name></country><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Funk, Natalja" sort="Funk, Natalja" uniqKey="Funk N" first="Natalja" last="Funk">Natalja Funk</name></region><name sortKey="Biskup, Saskia" sort="Biskup, Saskia" uniqKey="Biskup S" first="Saskia" last="Biskup">Saskia Biskup</name><name sortKey="Ott, Thomas" sort="Ott, Thomas" uniqKey="Ott T" first="Thomas" last="Ott">Thomas Ott</name><name sortKey="Riess, Olaf" sort="Riess, Olaf" uniqKey="Riess O" first="Olaf" last="Riess">Olaf Riess</name></country><country name="Suède"><region name="Svealand"><name sortKey="Galter, Dagmar" sort="Galter, Dagmar" uniqKey="Galter D" first="Dagmar" last="Galter">Dagmar Galter</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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