Movement Disorders (revue)

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In vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers

Identifieur interne : 000053 ( Pmc/Checkpoint ); précédent : 000052; suivant : 000054

In vivo dopaminergic and serotonergic dysfunction in DCTN1 gene mutation carriers

Auteurs : Andre C. Felicio [Canada] ; Katherine Dinelle [Canada] ; Pankaj A. Agarwal [Canada] ; Jessamyn Mckenzie [Canada] ; Nicole Heffernan [Canada] ; Jeremy D. Road [Canada] ; Silke Appel-Cresswell [Canada] ; Zbigniew K. Wszolek [États-Unis] ; Matthew J. Farrer [Canada] ; Michael Schulzer [Canada] ; Vesna Sossi [Canada] ; A. Jon Stoessl [Canada]

Source :

RBID : PMC:4139463

Abstract

Introduction

We have used positron emission tomography (PET) to assess dopaminergic and serotonergic terminal density in three subjects carrying a mutation in the DCT1 gene, two clinically affected with Perry syndrome.

Methods

All subjects had brain imaging using 18F-6-fluoro-L-dopa (FDOPA, dopamine synthesis and storage), (+)-11C-dihydrotetrabenazine (DTBZ, vesicular monoamine transporter type 2), and 11C-raclopride (RAC, dopamine D2/D3 receptors). One subject also underwent PET with 11C-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB, serotonin transporter).

Results

FDOPA-PET and DTBZ-PET in the affected individuals showed a reduction of striatal tracer uptake. Also, RAC-PET showed higher uptake in these area. DASB-PET showed significant uptake changes in left orbitofrontal cortex, bilateral anterior insula, left dorsolateral prefrontal cortex, left orbitofrontal cortex, left posterior cingulate cortex, left caudate and left ventral striatum.

Conclusions

Our data showed evidence of both striatal dopaminergic and widespread cortical/subcortical serotonergic dysfunctions in individuals carrying a mutation in the DCTN1 gene.


Url:
DOI: 10.1002/mds.25893
PubMed: 24797316
PubMed Central: 4139463


Affiliations:


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PMC:4139463

Le document en format XML

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dopaminergic and serotonergic dysfunction in
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<title>Introduction</title>
<p id="P1">We have used positron emission tomography (PET) to assess dopaminergic and serotonergic terminal density in three subjects carrying a mutation in the DCT1 gene, two clinically affected with Perry syndrome.</p>
</sec>
<sec id="S2">
<title>Methods</title>
<p id="P2">All subjects had brain imaging using 18F-6-fluoro-L-dopa (FDOPA, dopamine synthesis and storage), (+)-11C-dihydrotetrabenazine (DTBZ, vesicular monoamine transporter type 2), and 11C-raclopride (RAC, dopamine D2/D3 receptors). One subject also underwent PET with 11C-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB, serotonin transporter).</p>
</sec>
<sec id="S3">
<title>Results</title>
<p id="P3">FDOPA-PET and DTBZ-PET in the affected individuals showed a reduction of striatal tracer uptake. Also, RAC-PET showed higher uptake in these area. DASB-PET showed significant uptake changes in left orbitofrontal cortex, bilateral anterior insula, left dorsolateral prefrontal cortex, left orbitofrontal cortex, left posterior cingulate cortex, left caudate and left ventral striatum.</p>
</sec>
<sec id="S4">
<title>Conclusions</title>
<p id="P4">Our data showed evidence of both striatal dopaminergic and widespread cortical/subcortical serotonergic dysfunctions in individuals carrying a mutation in the
<italic>DCTN1</italic>
gene.</p>
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<italic>In vivo</italic>
dopaminergic and serotonergic dysfunction in
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gene mutation carriers</article-title>
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<contrib contrib-type="author">
<name>
<surname>Felicio</surname>
<given-names>Andre C.</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Dinelle</surname>
<given-names>Katherine</given-names>
</name>
<degrees>MSc</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Agarwal</surname>
<given-names>Pankaj A.</given-names>
</name>
<degrees>MD, DNB, DM</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>McKenzie</surname>
<given-names>Jessamyn</given-names>
</name>
<degrees>LPN</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Heffernan</surname>
<given-names>Nicole</given-names>
</name>
<degrees>RN</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Road</surname>
<given-names>Jeremy D.</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A2">2</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Appel-Cresswell</surname>
<given-names>Silke</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Wszolek</surname>
<given-names>Zbigniew K.</given-names>
</name>
<degrees>MD</degrees>
<xref ref-type="aff" rid="A3">3</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Farrer</surname>
<given-names>Matthew J.</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Schulzer</surname>
<given-names>Michael</given-names>
</name>
<degrees>MD, PhD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Sossi</surname>
<given-names>Vesna</given-names>
</name>
<degrees>PhD</degrees>
<xref ref-type="aff" rid="A1">1</xref>
</contrib>
<contrib contrib-type="author">
<name>
<surname>Stoessl</surname>
<given-names>A. Jon</given-names>
</name>
<degrees>CM, MD, FRCPC</degrees>
<xref ref-type="aff" rid="A1">1</xref>
<xref ref-type="corresp" rid="cor1">*</xref>
</contrib>
</contrib-group>
<aff id="A1">Pacific Parkinson's Research Centre, University of British Columbia, 2221 Wesbrook Mall, Vancouver, BC, Canada</aff>
<aff id="A2">Division of Respiratory Medicine, Department of Medicine, University of British Columbia, 2775 Laurel Street, Vancouver, BC, Canada</aff>
<aff id="A3">Department of Neurology, Mayo Clinic Jacksonville, 4500 San Pablo Road, Jacksonville, FL, USA</aff>
<author-notes>
<corresp id="cor1">
<label>*</label>
<bold>Correspondence to:</bold>
Dr. A. Jon Stoessl Correspondence at Pacific Parkinson's Research Centre, University of British Columbia, 2221 Wesbrook Mall, Vancouver, BC, Canada Tel.: +1 604 8227967; fax: +1 604 8227866.
<email>jstoessl@mail.ubc.ca</email>
</corresp>
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<pub-date pub-type="nihms-submitted">
<day>18</day>
<month>5</month>
<year>2014</year>
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<month>5</month>
<year>2014</year>
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<pub-date pub-type="ppub">
<month>8</month>
<year>2014</year>
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<day>01</day>
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<volume>29</volume>
<issue>9</issue>
<fpage>1197</fpage>
<lpage>1201</lpage>
<pmc-comment>elocation-id from pubmed: 10.1002/mds.25893</pmc-comment>
<abstract>
<sec id="S1">
<title>Introduction</title>
<p id="P1">We have used positron emission tomography (PET) to assess dopaminergic and serotonergic terminal density in three subjects carrying a mutation in the DCT1 gene, two clinically affected with Perry syndrome.</p>
</sec>
<sec id="S2">
<title>Methods</title>
<p id="P2">All subjects had brain imaging using 18F-6-fluoro-L-dopa (FDOPA, dopamine synthesis and storage), (+)-11C-dihydrotetrabenazine (DTBZ, vesicular monoamine transporter type 2), and 11C-raclopride (RAC, dopamine D2/D3 receptors). One subject also underwent PET with 11C-3-amino-4-(2-dimethylaminomethyl-phenylsulfanyl)-benzonitrile (DASB, serotonin transporter).</p>
</sec>
<sec id="S3">
<title>Results</title>
<p id="P3">FDOPA-PET and DTBZ-PET in the affected individuals showed a reduction of striatal tracer uptake. Also, RAC-PET showed higher uptake in these area. DASB-PET showed significant uptake changes in left orbitofrontal cortex, bilateral anterior insula, left dorsolateral prefrontal cortex, left orbitofrontal cortex, left posterior cingulate cortex, left caudate and left ventral striatum.</p>
</sec>
<sec id="S4">
<title>Conclusions</title>
<p id="P4">Our data showed evidence of both striatal dopaminergic and widespread cortical/subcortical serotonergic dysfunctions in individuals carrying a mutation in the
<italic>DCTN1</italic>
gene.</p>
</sec>
</abstract>
<kwd-group>
<kwd>Perry syndrome</kwd>
<kwd>dynactin gene</kwd>
<kwd>positron emission tomography</kwd>
<kwd>dopaminergic dysfunction</kwd>
<kwd>serotonergic dysfunction</kwd>
</kwd-group>
</article-meta>
</front>
</pmc>
<affiliations>
<list>
<country>
<li>Canada</li>
<li>États-Unis</li>
</country>
<region>
<li>Floride</li>
</region>
</list>
<tree>
<country name="Canada">
<noRegion>
<name sortKey="Felicio, Andre C" sort="Felicio, Andre C" uniqKey="Felicio A" first="Andre C." last="Felicio">Andre C. Felicio</name>
</noRegion>
<name sortKey="Agarwal, Pankaj A" sort="Agarwal, Pankaj A" uniqKey="Agarwal P" first="Pankaj A." last="Agarwal">Pankaj A. Agarwal</name>
<name sortKey="Appel Cresswell, Silke" sort="Appel Cresswell, Silke" uniqKey="Appel Cresswell S" first="Silke" last="Appel-Cresswell">Silke Appel-Cresswell</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="Heffernan, Nicole" sort="Heffernan, Nicole" uniqKey="Heffernan N" first="Nicole" last="Heffernan">Nicole Heffernan</name>
<name sortKey="Mckenzie, Jessamyn" sort="Mckenzie, Jessamyn" uniqKey="Mckenzie J" first="Jessamyn" last="Mckenzie">Jessamyn Mckenzie</name>
<name sortKey="Road, Jeremy D" sort="Road, Jeremy D" uniqKey="Road J" first="Jeremy D." last="Road">Jeremy D. Road</name>
<name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</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>
</country>
<country name="États-Unis">
<region name="Floride">
<name sortKey="Wszolek, Zbigniew K" sort="Wszolek, Zbigniew K" uniqKey="Wszolek Z" first="Zbigniew K." last="Wszolek">Zbigniew K. Wszolek</name>
</region>
</country>
</tree>
</affiliations>
</record>

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