Age-related decreased inhibitory vs. excitatory gene expression in the adult autistic brain
Identifieur interne : 002128 ( Ncbi/Merge ); précédent : 002127; suivant : 002129Age-related decreased inhibitory vs. excitatory gene expression in the adult autistic brain
Auteurs : Louie N. Van De Lagemaat [Royaume-Uni] ; Bonnie Nijhof [Pays-Bas] ; Daniëlle G. M. Bosch [Pays-Bas] ; Mahdokht Kohansal-Nodehi [Allemagne] ; Shivakumar Keerthikumar [Australie] ; J. Alexander Heimel [Pays-Bas]Source :
- Frontiers in Neuroscience [ 1662-4548 ] ; 2014.
Abstract
Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction and communication, and restricted behavior and interests. A disruption in the balance of excitatory and inhibitory neurotransmission has been hypothesized to underlie these disorders. Here we demonstrate that genes of both pathways are affected by ASD, and that gene expression of inhibitory and excitatory genes is altered in the cerebral cortex of adult but not younger autistic individuals. We have developed a measure for the difference in the level of excitation and inhibition based on gene expression and observe that in this measure inhibition is decreased relative to excitation in adult ASD compared to control. This difference was undetectable in young autistic brains. Given that many psychiatric features of autism are already present at an early age, this suggests that the observed imbalance in gene expression is an aging phenomenon in ASD rather than its underlying cause.
Url:
DOI: 10.3389/fnins.2014.00394
PubMed: 25538548
PubMed Central: 4259106
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Bosch</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Human Genetics, Radboud University Medical Center</institution><country>Nijmegen, Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea><wicri:noRegion>Bloemfontein 9301</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Bartiméus, Institute for the Visually Impaired</institution><country>Zeist, Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea><wicri:noRegion>Bloemfontein 9301</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Radboud Institute for Molecular Life Science, Radboud University Medical Center</institution><country>Nijmegen, Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea><wicri:noRegion>Bloemfontein 9301</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center</institution><country>Nijmegen, Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea><wicri:noRegion>Bloemfontein 9301</wicri:noRegion></affiliation></author><author><name sortKey="Kohansal Nodehi, Mahdokht" sort="Kohansal Nodehi, Mahdokht" uniqKey="Kohansal Nodehi M" first="Mahdokht" last="Kohansal-Nodehi">Mahdokht Kohansal-Nodehi</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Department of Neurobiology, Max Planck Institute for Biophysical Chemistry</institution><country>Göttingen, Germany</country></nlm:aff><country xml:lang="fr">Allemagne</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea><wicri:noRegion>Bloemfontein 9301</wicri:noRegion><wicri:noRegion>Bloemfontein 9301</wicri:noRegion><wicri:noRegion>Bloemfontein 9301</wicri:noRegion></affiliation></author><author><name sortKey="Keerthikumar, Shivakumar" sort="Keerthikumar, Shivakumar" uniqKey="Keerthikumar S" first="Shivakumar" last="Keerthikumar">Shivakumar Keerthikumar</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Department of Biochemistry, La Trobe Institute for Molecular Science 1, La Trobe University</institution><country>Melbourne, VIC, Australia</country></nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea><wicri:noRegion>Bloemfontein 9301</wicri:noRegion></affiliation></author><author><name sortKey="Heimel, J Alexander" sort="Heimel, J Alexander" uniqKey="Heimel J" first="J. Alexander" last="Heimel">J. Alexander Heimel</name><affiliation wicri:level="1"><nlm:aff id="aff8"><institution>Cortical Structure and Function Group, Netherlands Institute for Neuroscience</institution><country>Amsterdam, Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Department of Medical Microbiology and Virology, National Health Laboratory Service/University of the Free State, Bloemfontein 9301</wicri:regionArea><wicri:noRegion>Bloemfontein 9301</wicri:noRegion></affiliation></author></analytic><series><title level="j">Frontiers in Neuroscience</title><idno type="ISSN">1662-4548</idno><idno type="eISSN">1662-453X</idno><imprint><date when="2014">2014</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction and communication, and restricted behavior and interests. A disruption in the balance of excitatory and inhibitory neurotransmission has been hypothesized to underlie these disorders. Here we demonstrate that genes of both pathways are affected by ASD, and that gene expression of inhibitory and excitatory genes is altered in the cerebral cortex of adult but not younger autistic individuals. We have developed a measure for the difference in the level of excitation and inhibition based on gene expression and observe that in this measure inhibition is decreased relative to excitation in adult ASD compared to control. This difference was undetectable in young autistic brains. Given that many psychiatric features of autism are already present at an early age, this suggests that the observed imbalance in gene expression is an aging phenomenon in ASD rather than its underlying cause.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Baroncelli, L" uniqKey="Baroncelli L">L. 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<front><journal-meta><journal-id journal-id-type="nlm-ta">Front Neurosci</journal-id><journal-id journal-id-type="iso-abbrev">Front Neurosci</journal-id><journal-id journal-id-type="publisher-id">Front. Neurosci.</journal-id><journal-title-group><journal-title>Frontiers in Neuroscience</journal-title></journal-title-group><issn pub-type="ppub">1662-4548</issn><issn pub-type="epub">1662-453X</issn><publisher><publisher-name>Frontiers Media S.A.</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="pmid">25538548</article-id><article-id pub-id-type="pmc">4259106</article-id><article-id pub-id-type="doi">10.3389/fnins.2014.00394</article-id><article-categories><subj-group subj-group-type="heading"><subject>Genetics</subject><subj-group><subject>Original Research Article</subject></subj-group></subj-group></article-categories><title-group><article-title>Age-related decreased inhibitory vs. excitatory gene expression in the adult autistic brain</article-title></title-group><contrib-group><contrib contrib-type="author"><name><surname>van de Lagemaat</surname><given-names>Louie N.</given-names></name><xref ref-type="aff" rid="aff1"><sup>1</sup></xref><xref ref-type="author-notes" rid="fn001"><sup>*</sup></xref><uri xlink:type="simple" xlink:href="http://community.frontiersin.org/people/u/72113"></uri></contrib><contrib contrib-type="author"><name><surname>Nijhof</surname><given-names>Bonnie</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="author-notes" rid="fn003"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Bosch</surname><given-names>Daniëlle G. M.</given-names></name><xref ref-type="aff" rid="aff2"><sup>2</sup></xref><xref ref-type="aff" rid="aff3"><sup>3</sup></xref><xref ref-type="aff" rid="aff4"><sup>4</sup></xref><xref ref-type="aff" rid="aff5"><sup>5</sup></xref><xref ref-type="author-notes" rid="fn003"><sup>†</sup></xref></contrib><contrib contrib-type="author"><name><surname>Kohansal-Nodehi</surname><given-names>Mahdokht</given-names></name><xref ref-type="aff" rid="aff6"><sup>6</sup></xref><xref ref-type="author-notes" rid="fn003"><sup>†</sup></xref><uri xlink:type="simple" xlink:href="http://community.frontiersin.org/people/u/196389"></uri></contrib><contrib contrib-type="author"><name><surname>Keerthikumar</surname><given-names>Shivakumar</given-names></name><xref ref-type="aff" rid="aff7"><sup>7</sup></xref><xref ref-type="author-notes" rid="fn003"><sup>†</sup></xref><uri xlink:type="simple" xlink:href="http://community.frontiersin.org/people/u/195004"></uri></contrib><contrib contrib-type="author"><name><surname>Heimel</surname><given-names>J. Alexander</given-names></name><xref ref-type="aff" rid="aff8"><sup>8</sup></xref><uri xlink:type="simple" xlink:href="http://community.frontiersin.org/people/u/38606"></uri></contrib></contrib-group><aff id="aff1"><sup>1</sup><institution>Centre for Neuroregeneration and Centre for Clinical Brain Sciences, University of Edinburgh</institution><country>Edinburgh, UK</country></aff><aff id="aff2"><sup>2</sup><institution>Department of Human Genetics, Radboud University Medical Center</institution><country>Nijmegen, Netherlands</country></aff><aff id="aff3"><sup>3</sup><institution>Bartiméus, Institute for the Visually Impaired</institution><country>Zeist, Netherlands</country></aff><aff id="aff4"><sup>4</sup><institution>Radboud Institute for Molecular Life Science, Radboud University Medical Center</institution><country>Nijmegen, Netherlands</country></aff><aff id="aff5"><sup>5</sup><institution>Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center</institution><country>Nijmegen, Netherlands</country></aff><aff id="aff6"><sup>6</sup><institution>Department of Neurobiology, Max Planck Institute for Biophysical Chemistry</institution><country>Göttingen, Germany</country></aff><aff id="aff7"><sup>7</sup><institution>Department of Biochemistry, La Trobe Institute for Molecular Science 1, La Trobe University</institution><country>Melbourne, VIC, Australia</country></aff><aff id="aff8"><sup>8</sup><institution>Cortical Structure and Function Group, Netherlands Institute for Neuroscience</institution><country>Amsterdam, Netherlands</country></aff><author-notes><fn fn-type="edited-by"><p>Edited by: Robert W. Williams, University of Tennessee Health Science Center, USA</p></fn><fn fn-type="edited-by"><p>Reviewed by: Detlef H. Heck, University of Tennessee Health Science Center, USA; Khyobeni Mozhui, University of Tennessee Health Science Center, USA</p></fn><corresp id="fn001">*Correspondence: Louie N. van de Lagemaat, Centre for Neuroregeneration and Centre for Clinical Brain Sciences, University of Edinburgh, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK e-mail: <email xlink:type="simple">louie.van.de.lagemaat@ed.ac.uk</email></corresp><fn fn-type="other" id="fn002"><p>This article was submitted to Neurogenomics, a section of the journal Frontiers in Neuroscience.</p></fn><fn fn-type="present-address" id="fn003"><p>†These authors have contributed equally to this work.</p></fn></author-notes><pub-date pub-type="epub"><day>08</day><month>12</month><year>2014</year></pub-date><pub-date pub-type="collection"><year>2014</year></pub-date><volume>8</volume><elocation-id>394</elocation-id><history><date date-type="received"><day>17</day><month>9</month><year>2014</year></date><date date-type="accepted"><day>18</day><month>11</month><year>2014</year></date></history><permissions><copyright-statement>Copyright © 2014 van de Lagemaat, Nijhof, Bosch, Kohansal-Nodehi, Keerthikumar and Heimel.</copyright-statement><copyright-year>2014</copyright-year><license license-type="open-access" xlink:href="http://creativecommons.org/licenses/by/4.0/"><license-p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</license-p></license></permissions><abstract><p>Autism spectrum disorders (ASDs) are neurodevelopmental disorders characterized by impaired social interaction and communication, and restricted behavior and interests. A disruption in the balance of excitatory and inhibitory neurotransmission has been hypothesized to underlie these disorders. Here we demonstrate that genes of both pathways are affected by ASD, and that gene expression of inhibitory and excitatory genes is altered in the cerebral cortex of adult but not younger autistic individuals. We have developed a measure for the difference in the level of excitation and inhibition based on gene expression and observe that in this measure inhibition is decreased relative to excitation in adult ASD compared to control. This difference was undetectable in young autistic brains. Given that many psychiatric features of autism are already present at an early age, this suggests that the observed imbalance in gene expression is an aging phenomenon in ASD rather than its underlying cause.</p></abstract><kwd-group><kwd>autism</kwd><kwd>excitation</kwd><kwd>inhibition</kwd><kwd>balance</kwd><kwd>gene expression</kwd><kwd>age effect</kwd></kwd-group><counts><fig-count count="2"></fig-count><table-count count="3"></table-count><equation-count count="0"></equation-count><ref-count count="35"></ref-count><page-count count="9"></page-count><word-count count="6442"></word-count></counts></article-meta></front></pmc><affiliations><list><country><li>Allemagne</li><li>Australie</li><li>Pays-Bas</li><li>Royaume-Uni</li></country></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Van De Lagemaat, Louie N" sort="Van De Lagemaat, Louie N" uniqKey="Van De Lagemaat L" first="Louie N." last="Van De Lagemaat">Louie N. Van De Lagemaat</name></noRegion></country><country name="Pays-Bas"><noRegion><name sortKey="Nijhof, Bonnie" sort="Nijhof, Bonnie" uniqKey="Nijhof B" first="Bonnie" last="Nijhof">Bonnie Nijhof</name></noRegion><name sortKey="Bosch, Danielle G M" sort="Bosch, Danielle G M" uniqKey="Bosch D" first="Daniëlle G. M." last="Bosch">Daniëlle G. M. Bosch</name><name sortKey="Bosch, Danielle G M" sort="Bosch, Danielle G M" uniqKey="Bosch D" first="Daniëlle G. M." last="Bosch">Daniëlle G. M. Bosch</name><name sortKey="Bosch, Danielle G M" sort="Bosch, Danielle G M" uniqKey="Bosch D" first="Daniëlle G. M." last="Bosch">Daniëlle G. M. Bosch</name><name sortKey="Bosch, Danielle G M" sort="Bosch, Danielle G M" uniqKey="Bosch D" first="Daniëlle G. M." last="Bosch">Daniëlle G. M. Bosch</name><name sortKey="Heimel, J Alexander" sort="Heimel, J Alexander" uniqKey="Heimel J" first="J. Alexander" last="Heimel">J. Alexander Heimel</name></country><country name="Allemagne"><noRegion><name sortKey="Kohansal Nodehi, Mahdokht" sort="Kohansal Nodehi, Mahdokht" uniqKey="Kohansal Nodehi M" first="Mahdokht" last="Kohansal-Nodehi">Mahdokht Kohansal-Nodehi</name></noRegion></country><country name="Australie"><noRegion><name sortKey="Keerthikumar, Shivakumar" sort="Keerthikumar, Shivakumar" uniqKey="Keerthikumar S" first="Shivakumar" last="Keerthikumar">Shivakumar Keerthikumar</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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