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Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance
BACKGROUND: Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synap...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825256/ https://www.ncbi.nlm.nih.gov/pubmed/20179754 http://dx.doi.org/10.1371/journal.pone.0009348 |
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author | Bertolino, Alessandro Taurisano, Paolo Pisciotta, Nicola Marco Blasi, Giuseppe Fazio, Leonardo Romano, Raffaella Gelao, Barbara Bianco, Luciana Lo Lozupone, Madia Di Giorgio, Annabella Caforio, Grazia Sambataro, Fabio Niccoli-Asabella, Artor Papp, Audrey Ursini, Gianluca Sinibaldi, Lorenzo Popolizio, Teresa Sadee, Wolfgang Rubini, Giuseppe |
author_facet | Bertolino, Alessandro Taurisano, Paolo Pisciotta, Nicola Marco Blasi, Giuseppe Fazio, Leonardo Romano, Raffaella Gelao, Barbara Bianco, Luciana Lo Lozupone, Madia Di Giorgio, Annabella Caforio, Grazia Sambataro, Fabio Niccoli-Asabella, Artor Papp, Audrey Ursini, Gianluca Sinibaldi, Lorenzo Popolizio, Teresa Sadee, Wolfgang Rubini, Giuseppe |
author_sort | Bertolino, Alessandro |
collection | PubMed |
description | BACKGROUND: Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. METHODS: Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [(123)I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [(123)I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. RESULTS: Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [(123)I]IBZM and of [(123)I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. CONCLUSIONS: Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway. |
format | Text |
id | pubmed-2825256 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-28252562010-02-24 Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance Bertolino, Alessandro Taurisano, Paolo Pisciotta, Nicola Marco Blasi, Giuseppe Fazio, Leonardo Romano, Raffaella Gelao, Barbara Bianco, Luciana Lo Lozupone, Madia Di Giorgio, Annabella Caforio, Grazia Sambataro, Fabio Niccoli-Asabella, Artor Papp, Audrey Ursini, Gianluca Sinibaldi, Lorenzo Popolizio, Teresa Sadee, Wolfgang Rubini, Giuseppe PLoS One Research Article BACKGROUND: Variation of the gene coding for D2 receptors (DRD2) has been associated with risk for schizophrenia and with working memory deficits. A functional intronic SNP (rs1076560) predicts relative expression of the two D2 receptors isoforms, D2S (mainly pre-synaptic) and D2L (mainly post-synaptic). However, the effect of functional genetic variation of DRD2 on striatal dopamine D2 signaling and on its correlation with prefrontal activity during working memory in humans is not known. METHODS: Thirty-seven healthy subjects were genotyped for rs1076560 (G>T) and underwent SPECT with [(123)I]IBZM (which binds primarily to post-synaptic D2 receptors) and with [(123)I]FP-CIT (which binds to pre-synaptic dopamine transporters, whose activity and density is also regulated by pre-synaptic D2 receptors), as well as BOLD fMRI during N-Back working memory. RESULTS: Subjects carrying the T allele (previously associated with reduced D2S expression) had striatal reductions of [(123)I]IBZM and of [(123)I]FP-CIT binding. DRD2 genotype also differentially predicted the correlation between striatal dopamine D2 signaling (as identified with factor analysis of the two radiotracers) and activity of the prefrontal cortex during working memory as measured with BOLD fMRI, which was positive in GG subjects and negative in GT. CONCLUSIONS: Our results demonstrate that this functional SNP within DRD2 predicts striatal binding of the two radiotracers to dopamine transporters and D2 receptors as well as the correlation between striatal D2 signaling with prefrontal cortex activity during performance of a working memory task. These data are consistent with the possibility that the balance of excitatory/inhibitory modulation of striatal neurons may also affect striatal outputs in relationship with prefrontal activity during working memory performance within the cortico-striatal-thalamic-cortical pathway. Public Library of Science 2010-02-22 /pmc/articles/PMC2825256/ /pubmed/20179754 http://dx.doi.org/10.1371/journal.pone.0009348 Text en Bertolino et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Bertolino, Alessandro Taurisano, Paolo Pisciotta, Nicola Marco Blasi, Giuseppe Fazio, Leonardo Romano, Raffaella Gelao, Barbara Bianco, Luciana Lo Lozupone, Madia Di Giorgio, Annabella Caforio, Grazia Sambataro, Fabio Niccoli-Asabella, Artor Papp, Audrey Ursini, Gianluca Sinibaldi, Lorenzo Popolizio, Teresa Sadee, Wolfgang Rubini, Giuseppe Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance |
title | Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance |
title_full | Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance |
title_fullStr | Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance |
title_full_unstemmed | Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance |
title_short | Genetically Determined Measures of Striatal D2 Signaling Predict Prefrontal Activity during Working Memory Performance |
title_sort | genetically determined measures of striatal d2 signaling predict prefrontal activity during working memory performance |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825256/ https://www.ncbi.nlm.nih.gov/pubmed/20179754 http://dx.doi.org/10.1371/journal.pone.0009348 |
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