Chronic SSRI Treatment Exacerbates Serotonin Deficiency in Humanized Tph2 Mutant Mice
Identifieur interne : 001362 ( Ncbi/Merge ); précédent : 001361; suivant : 001363Chronic SSRI Treatment Exacerbates Serotonin Deficiency in Humanized Tph2 Mutant Mice
Auteurs : William X0a B. Siesser [États-Unis] ; Benjamin D. Sachs [États-Unis] ; Amy J. Ramsey [Canada] ; Tatyana D. Sotnikova [Italie] ; Jean-Martin Beaulieu [Canada] ; Xiaodong Zhang [Singapour, États-Unis] ; Marc G. Caron [États-Unis] ; Raul R. Gainetdinov [États-Unis, Italie]Source :
- ACS Chemical Neuroscience [ 1948-7193 ] ; 2012.
Abstract
Selective serotonin reuptake inhibitors (SSRIs) are a
major class
of antidepressants that act by blocking inward transport of serotonin
(5-HT) into presynaptic neurons mediated by the serotonin transporter
(SERT). Both reuptake and ongoing synthesis are essential in supporting
intraneuronal serotonin concentrations in serotonergic neurons. A
rare mutation in tryptophan hydroxylase 2 (
Url:
DOI: 10.1021/cn300127h
PubMed: 23336047
PubMed Central: 3547473
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PMC:3547473Le document en format XML
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Sotnikova</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Neuroscience and Brain Technologies,<institution>Istituto Italiano di Tecnologia</institution> (IIT), Via Morego 30, Genova, 16163 Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> (IIT), Via Morego 30, Genova</wicri:regionArea><wicri:noRegion>Genova</wicri:noRegion></affiliation></author><author><name sortKey="Beaulieu, Jean Martin" sort="Beaulieu, Jean Martin" uniqKey="Beaulieu J" first="Jean-Martin" last="Beaulieu">Jean-Martin Beaulieu</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Psychiatry and Neuroscience,<institution>Université Laval/IUSMQ</institution>, Québec, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Xiaodong" sort="Zhang, Xiaodong" uniqKey="Zhang X" first="Xiaodong" last="Zhang">Xiaodong Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff5">Neuroscience & Behavioral Disorders Program,<institution>Duke−NUS Graduate Medical School Singapore</institution>, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea></wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Physiology,<institution>National University of Singapore</institution>, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea></wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Department of Psychiatry and Behavioral Sciences,<institution>Duke University Medical Center</institution>, Durham, North Carolina 27710, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, Durham, North Carolina 27710</wicri:regionArea><wicri:noRegion>North Carolina 27710</wicri:noRegion></affiliation></author><author><name sortKey="Caron, Marc G" sort="Caron, Marc G" uniqKey="Caron M" first="Marc G." last="Caron">Marc G. 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Gainetdinov</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cell Biology,<institution>Duke University</institution>, Durham, North Carolina 27710, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, Durham, North Carolina 27710</wicri:regionArea><wicri:noRegion>North Carolina 27710</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Neuroscience and Brain Technologies,<institution>Istituto Italiano di Tecnologia</institution> (IIT), Via Morego 30, Genova, 16163 Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> (IIT), Via Morego 30, Genova</wicri:regionArea><wicri:noRegion>Genova</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PMC</idno><idno type="pmid">23336047</idno><idno type="pmc">3547473</idno><idno type="url">http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3547473</idno><idno type="RBID">PMC:3547473</idno><idno type="doi">10.1021/cn300127h</idno><date when="2012">2012</date><idno type="wicri:Area/Pmc/Corpus">000183</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Corpus" wicri:corpus="PMC">000183</idno><idno type="wicri:Area/Pmc/Curation">000183</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Curation">000183</idno><idno type="wicri:Area/Pmc/Checkpoint">000854</idno><idno type="wicri:explorRef" wicri:stream="Pmc" wicri:step="Checkpoint">000854</idno><idno type="wicri:Area/Ncbi/Merge">001362</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Chronic SSRI Treatment
Exacerbates Serotonin Deficiency
in Humanized <italic>Tph2</italic> Mutant Mice</title><author><name sortKey="Siesser, William X0a B" sort="Siesser, William X0a B" uniqKey="Siesser W" first="William X0a B." last="Siesser">William X0a B. Siesser</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cell Biology,<institution>Duke University</institution>, Durham, North Carolina 27710, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, Durham, North Carolina 27710</wicri:regionArea><wicri:noRegion>North Carolina 27710</wicri:noRegion></affiliation></author><author><name sortKey="Sachs, Benjamin D" sort="Sachs, Benjamin D" uniqKey="Sachs B" first="Benjamin D." last="Sachs">Benjamin D. Sachs</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cell Biology,<institution>Duke University</institution>, Durham, North Carolina 27710, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, Durham, North Carolina 27710</wicri:regionArea><wicri:noRegion>North Carolina 27710</wicri:noRegion></affiliation></author><author><name sortKey="Ramsey, Amy J" sort="Ramsey, Amy J" uniqKey="Ramsey A" first="Amy J." last="Ramsey">Amy J. Ramsey</name><affiliation wicri:level="1"><nlm:aff id="aff2">Department of Pharmacology and Toxicology,<institution>University of Toronto</institution>, ON, Canada M5S 1A8</nlm:aff><country>Canada</country><wicri:regionArea>, ON</wicri:regionArea><wicri:noRegion>ON</wicri:noRegion></affiliation></author><author><name sortKey="Sotnikova, Tatyana D" sort="Sotnikova, Tatyana D" uniqKey="Sotnikova T" first="Tatyana D." last="Sotnikova">Tatyana D. Sotnikova</name><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Neuroscience and Brain Technologies,<institution>Istituto Italiano di Tecnologia</institution> (IIT), Via Morego 30, Genova, 16163 Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> (IIT), Via Morego 30, Genova</wicri:regionArea><wicri:noRegion>Genova</wicri:noRegion></affiliation></author><author><name sortKey="Beaulieu, Jean Martin" sort="Beaulieu, Jean Martin" uniqKey="Beaulieu J" first="Jean-Martin" last="Beaulieu">Jean-Martin Beaulieu</name><affiliation wicri:level="1"><nlm:aff id="aff4">Department of Psychiatry and Neuroscience,<institution>Université Laval/IUSMQ</institution>, Québec, Canada</nlm:aff><country xml:lang="fr">Canada</country><wicri:regionArea>, Québec</wicri:regionArea><wicri:noRegion>Québec</wicri:noRegion></affiliation></author><author><name sortKey="Zhang, Xiaodong" sort="Zhang, Xiaodong" uniqKey="Zhang X" first="Xiaodong" last="Zhang">Xiaodong Zhang</name><affiliation wicri:level="1"><nlm:aff id="aff5">Neuroscience & Behavioral Disorders Program,<institution>Duke−NUS Graduate Medical School Singapore</institution>, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea></wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff6">Department of Physiology,<institution>National University of Singapore</institution>, Singapore</nlm:aff><country xml:lang="fr">Singapour</country><wicri:regionArea></wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff7">Department of Psychiatry and Behavioral Sciences,<institution>Duke University Medical Center</institution>, Durham, North Carolina 27710, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, Durham, North Carolina 27710</wicri:regionArea><wicri:noRegion>North Carolina 27710</wicri:noRegion></affiliation></author><author><name sortKey="Caron, Marc G" sort="Caron, Marc G" uniqKey="Caron M" first="Marc G." last="Caron">Marc G. Caron</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cell Biology,<institution>Duke University</institution>, Durham, North Carolina 27710, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, Durham, North Carolina 27710</wicri:regionArea><wicri:noRegion>North Carolina 27710</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff8">Department of Neurobiology,<institution>Duke University Medical Center</institution>, Durham, North Carolina 27710, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, Durham, North Carolina 27710</wicri:regionArea><wicri:noRegion>North Carolina 27710</wicri:noRegion></affiliation></author><author><name sortKey="Gainetdinov, Raul R" sort="Gainetdinov, Raul R" uniqKey="Gainetdinov R" first="Raul R." last="Gainetdinov">Raul R. Gainetdinov</name><affiliation wicri:level="1"><nlm:aff id="aff1">Department of Cell Biology,<institution>Duke University</institution>, Durham, North Carolina 27710, United States</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>, Durham, North Carolina 27710</wicri:regionArea><wicri:noRegion>North Carolina 27710</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3">Department of Neuroscience and Brain Technologies,<institution>Istituto Italiano di Tecnologia</institution> (IIT), Via Morego 30, Genova, 16163 Italy</nlm:aff><country xml:lang="fr">Italie</country><wicri:regionArea> (IIT), Via Morego 30, Genova</wicri:regionArea><wicri:noRegion>Genova</wicri:noRegion></affiliation></author></analytic><series><title level="j">ACS Chemical Neuroscience</title><idno type="ISSN">1948-7193</idno><idno type="eISSN">1948-7193</idno><imprint><date when="2012">2012</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p content-type="toc-graphic"><graphic xlink:href="cn-2012-00127h_0005" id="ab-tgr1"></graphic></p><p>Selective serotonin reuptake inhibitors (SSRIs) are a
major class
of antidepressants that act by blocking inward transport of serotonin
(5-HT) into presynaptic neurons mediated by the serotonin transporter
(SERT). Both reuptake and ongoing synthesis are essential in supporting
intraneuronal serotonin concentrations in serotonergic neurons. A
rare mutation in tryptophan hydroxylase 2 (<italic>Tph2</italic>),
the rate limiting enzyme for 5-HT synthesis, was identified in several
patients with major depression, and knock-in mice expressing the analogous
mutation (R439H <italic>Tph2</italic> KI) show 80% reduction in 5-HT
synthesis and tissue levels. Chronic treatment with SSRIs (fluoxetine
and paroxetine) resulted in a dramatic further depletion of 5-HT tissue
levels in R439H <italic>Tph2</italic> KI mice (down to 1–3%
of wild type levels) while having little effects in wild-type controls.
Treatment with the 5-HT precursor 5-hydroxytryptophan (5-HTP) restored
5-HT tissue content in mutant mice, and cotreatment with 5-HTP and
fluoxetine essentially prevented the depleting effect of a chronic
SSRI. These data demonstrate that chronic SSRI treatment could further
exacerbate the 5-HT deficiency in <italic>Tph2</italic> mutation carriers,
and this can be prevented by 5-HTP supplementation.</p></div></front></TEI><pmc article-type="rapid-communication" xml:lang="EN"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
<front><journal-meta><journal-id journal-id-type="nlm-ta">ACS Chem Neurosci</journal-id><journal-id journal-id-type="iso-abbrev">ACS Chem Neurosci</journal-id><journal-id journal-id-type="publisher-id">cn</journal-id><journal-id journal-id-type="coden">acncdm</journal-id><journal-title-group><journal-title>ACS Chemical Neuroscience</journal-title></journal-title-group><issn pub-type="ppub">1948-7193</issn><issn pub-type="epub">1948-7193</issn><publisher><publisher-name>American Chemical
Society</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">23336047</article-id><article-id pub-id-type="pmc">3547473</article-id><article-id pub-id-type="doi">10.1021/cn300127h</article-id><article-categories><subj-group><subject>Letter</subject></subj-group></article-categories><title-group><article-title>Chronic SSRI Treatment
Exacerbates Serotonin Deficiency
in Humanized <italic>Tph2</italic> Mutant Mice</article-title></title-group><contrib-group><contrib contrib-type="author" id="ath1"><name><surname>Siesser</surname><given-names>William
B.</given-names></name><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" id="ath2"><name><surname>Sachs</surname><given-names>Benjamin D.</given-names></name><xref rid="aff1" ref-type="aff">†</xref></contrib><contrib contrib-type="author" id="ath3"><name><surname>Ramsey</surname><given-names>Amy J.</given-names></name><xref rid="aff2" ref-type="aff">‡</xref></contrib><contrib contrib-type="author" id="ath4"><name><surname>Sotnikova</surname><given-names>Tatyana D.</given-names></name><xref rid="aff3" ref-type="aff">§</xref></contrib><contrib contrib-type="author" id="ath5"><name><surname>Beaulieu</surname><given-names>Jean-Martin</given-names></name><xref rid="aff4" ref-type="aff">∥</xref></contrib><contrib contrib-type="author" id="ath6"><name><surname>Zhang</surname><given-names>Xiaodong</given-names></name><xref rid="aff5" ref-type="aff">⊥</xref><xref rid="aff6" ref-type="aff">#</xref><xref rid="aff7" ref-type="aff">▽</xref></contrib><contrib contrib-type="author" id="ath7"><name><surname>Caron</surname><given-names>Marc G.</given-names></name><xref rid="aff1" ref-type="aff">†</xref><xref rid="aff8" ref-type="aff">○</xref></contrib><contrib contrib-type="author" corresp="yes" id="ath8"><name><surname>Gainetdinov</surname><given-names>Raul R.</given-names></name><xref rid="cor1" ref-type="other">*</xref><xref rid="aff1" ref-type="aff">†</xref><xref rid="aff3" ref-type="aff">§</xref></contrib><aff id="aff1"><label>†</label>Department of Cell Biology,<institution>Duke University</institution>, Durham, North Carolina 27710, United States</aff><aff id="aff2"><label>‡</label>Department of Pharmacology and Toxicology,<institution>University of Toronto</institution>, ON, Canada M5S 1A8</aff><aff id="aff3"><label>§</label>Department of Neuroscience and Brain Technologies,<institution>Istituto Italiano di Tecnologia</institution> (IIT), Via Morego 30, Genova, 16163 Italy</aff><aff id="aff4"><label>∥</label>Department of Psychiatry and Neuroscience,<institution>Université Laval/IUSMQ</institution>, Québec, Canada</aff><aff id="aff5"><label>⊥</label>Neuroscience & Behavioral Disorders Program,<institution>Duke−NUS Graduate Medical School Singapore</institution>, Singapore</aff><aff id="aff6"><label>#</label>Department of Physiology,<institution>National University of Singapore</institution>, Singapore</aff><aff id="aff7"><label>▽</label>Department of Psychiatry and Behavioral Sciences,<institution>Duke University Medical Center</institution>, Durham, North Carolina 27710, United States</aff><aff id="aff8"><label>○</label>Department of Neurobiology,<institution>Duke University Medical Center</institution>, Durham, North Carolina 27710, United States</aff></contrib-group><author-notes><corresp id="cor1"><label>*</label>Mailing
address: Department of
Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia,
Via Morego 30, Genoa, 16167, Italy. Telephone: <phone>+39 010 71781513</phone>. E-mail: <email>raul.gainetdinov@iit.it</email>.</corresp></author-notes><pub-date pub-type="epub"><day>01</day><month>10</month><year>2012</year></pub-date><pub-date pub-type="collection"><day>16</day><month>01</month><year>2013</year></pub-date><volume>4</volume><issue>1</issue><issue-title>Celebrating
25 Years of the Serotonin Club</issue-title><fpage>84</fpage><lpage>88</lpage><history><date date-type="received"><day>13</day><month>08</month><year>2012</year></date><date date-type="accepted"><day>01</day><month>10</month><year>2012</year></date></history><permissions><copyright-statement>Copyright © 2012 American Chemical Society</copyright-statement><copyright-year>2012</copyright-year><copyright-holder>American Chemical Society</copyright-holder></permissions><abstract><p content-type="toc-graphic"><graphic xlink:href="cn-2012-00127h_0005" id="ab-tgr1"></graphic></p><p>Selective serotonin reuptake inhibitors (SSRIs) are a
major class
of antidepressants that act by blocking inward transport of serotonin
(5-HT) into presynaptic neurons mediated by the serotonin transporter
(SERT). Both reuptake and ongoing synthesis are essential in supporting
intraneuronal serotonin concentrations in serotonergic neurons. A
rare mutation in tryptophan hydroxylase 2 (<italic>Tph2</italic>),
the rate limiting enzyme for 5-HT synthesis, was identified in several
patients with major depression, and knock-in mice expressing the analogous
mutation (R439H <italic>Tph2</italic> KI) show 80% reduction in 5-HT
synthesis and tissue levels. Chronic treatment with SSRIs (fluoxetine
and paroxetine) resulted in a dramatic further depletion of 5-HT tissue
levels in R439H <italic>Tph2</italic> KI mice (down to 1–3%
of wild type levels) while having little effects in wild-type controls.
Treatment with the 5-HT precursor 5-hydroxytryptophan (5-HTP) restored
5-HT tissue content in mutant mice, and cotreatment with 5-HTP and
fluoxetine essentially prevented the depleting effect of a chronic
SSRI. These data demonstrate that chronic SSRI treatment could further
exacerbate the 5-HT deficiency in <italic>Tph2</italic> mutation carriers,
and this can be prevented by 5-HTP supplementation.</p></abstract><kwd-group><kwd>Tryptophan hydroxylase</kwd><kwd>serotonin</kwd><kwd>antidepressant</kwd><kwd>SSRI</kwd><kwd>depression</kwd><kwd>SNP</kwd></kwd-group><funding-group><funding-statement><funding-source>National Institutes of Health, United States</funding-source></funding-statement></funding-group><custom-meta-group><custom-meta><meta-name>document-id-old-9</meta-name><meta-value>cn300127h</meta-value></custom-meta><custom-meta><meta-name>document-id-new-14</meta-name><meta-value>cn-2012-00127h</meta-value></custom-meta><custom-meta><meta-name>ccc-price</meta-name><meta-value></meta-value></custom-meta></custom-meta-group></article-meta></front></pmc><affiliations><list><country><li>Canada</li><li>Italie</li><li>Singapour</li><li>États-Unis</li></country></list><tree><country name="États-Unis"><noRegion><name sortKey="Siesser, William X0a B" sort="Siesser, William X0a B" uniqKey="Siesser W" first="William X0a B." last="Siesser">William X0a B. Siesser</name></noRegion><name sortKey="Caron, Marc G" sort="Caron, Marc G" uniqKey="Caron M" first="Marc G." last="Caron">Marc G. Caron</name><name sortKey="Caron, Marc G" sort="Caron, Marc G" uniqKey="Caron M" first="Marc G." last="Caron">Marc G. Caron</name><name sortKey="Gainetdinov, Raul R" sort="Gainetdinov, Raul R" uniqKey="Gainetdinov R" first="Raul R." last="Gainetdinov">Raul R. Gainetdinov</name><name sortKey="Sachs, Benjamin D" sort="Sachs, Benjamin D" uniqKey="Sachs B" first="Benjamin D." last="Sachs">Benjamin D. Sachs</name><name sortKey="Zhang, Xiaodong" sort="Zhang, Xiaodong" uniqKey="Zhang X" first="Xiaodong" last="Zhang">Xiaodong Zhang</name></country><country name="Canada"><noRegion><name sortKey="Ramsey, Amy J" sort="Ramsey, Amy J" uniqKey="Ramsey A" first="Amy J." last="Ramsey">Amy J. Ramsey</name></noRegion><name sortKey="Beaulieu, Jean Martin" sort="Beaulieu, Jean Martin" uniqKey="Beaulieu J" first="Jean-Martin" last="Beaulieu">Jean-Martin Beaulieu</name></country><country name="Italie"><noRegion><name sortKey="Sotnikova, Tatyana D" sort="Sotnikova, Tatyana D" uniqKey="Sotnikova T" first="Tatyana D." last="Sotnikova">Tatyana D. Sotnikova</name></noRegion><name sortKey="Gainetdinov, Raul R" sort="Gainetdinov, Raul R" uniqKey="Gainetdinov R" first="Raul R." last="Gainetdinov">Raul R. Gainetdinov</name></country><country name="Singapour"><noRegion><name sortKey="Zhang, Xiaodong" sort="Zhang, Xiaodong" uniqKey="Zhang X" first="Xiaodong" last="Zhang">Xiaodong Zhang</name></noRegion><name sortKey="Zhang, Xiaodong" sort="Zhang, Xiaodong" uniqKey="Zhang X" first="Xiaodong" last="Zhang">Xiaodong Zhang</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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