| Zugriffsnummer | 39093 |
| Dokumenttyp | Zeitschriftenartikel |
| Peer Review | unbekannt |
| Sprache | Englisch |
| Titel | The Arf6 activator Efa6/PSD3 confers regional specificity and modulates ethanol consumption in Drosophila and humans |
| Autor(in); Institution |
Gonzalez, D.; Department of Psychiatry, Univ. of Texas, Dallas, TX, USA
Jia, T.; Institute of Psychiatry, King's College London, London, UK
Pinzón, J.; Department of Psychiatry, Univ. of Texas, Dallas, TX, USA
Acevedo, S.; Department of Psychiatry, Univ. of Texas, Dallas, TX, USA
Ojelade, S.; Department of Psychiatry, Univ. of Texas, Dallas, TX, USA
Xu, B.; Institute of Psychiatry, King's College London, London, UK
Tay, N; Institute of Psychiatry, King's College London, London, UK
Desrivières, S.; Institute of Psychiatry, King's College London, London, UK
Hernandez, J.; Department of Psychiatry, Molecular Medicine Program, Univ. of Utah, Salt Lake City, UT, USA
Banaschewski, T.; Department of Child and Adolescent Psychiatry, Central Institute of Mental Health, Mannheim, GERMANY
Büchel, A.; Universitätsklinikum Hamburg Eppendorf, Hamburg, GERMANY
Bokde, A.; Institute of Neuroscience, Trinity College Dublin, Dublin, IRELAND
Conrod, PJ; Department of Psychiatry, Universite de Montreal, Montreal, QC, CANADA
Flor, H.; Department of Cognitive and Clinical Neuroscience, Heidelberg Univ., Mannheim, GERMANY
Frouin, V.; Neurospin, Gif-sur-Yvette, FRANCE
Gallinat, J.; Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Berlin, GERMANY
Garavan, H.; Department of Psychiatry and Psychology, Univ. of Vermont, Burlington, VT, USA
Gowland, P.; Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, Univ. of Nottingham, Nottingham, UK
Heinz, A.; Department of Psychiatry and Psychotherapy, Campus Charite Mitte, Berlin , GERMANY
Ittermann, Bernd; 8.1, Biomedizinische Magnetresonanz, PTB-Berlin
Lathrop, M.; McGill University, Montreal, QC, CANADA
Martinot, J.-L.; Institut National de la Sante et de la Recherche Medicine, INSERM CEA Unit 1000, Univ. Paris Sud, Paris, FRANCE
Paus, T.; School of Psychology, University of Nottingham, Nottingham, UK
Smolka, M.N.; Department of Psychiatry and Psychotherapy, Technische Universität Dresden, Dresden, GERMANY
Rhodan, A.R.; Division of Nephrology, Department of Internal Medicine, Univ. of Texas, Dallas, TX, USA
Schumann, G.; Institute of Psychiatry, King's College London, London, UK
Rothenfluh, A.; Department of Psychiatry, Univ. of Texas, Dallas, TX, USA
|
| Quelle/Jahr | Molecular Psychiatry: 23 (2018), 3, 621 - 628 |
| ISSN | 1359-4184 (PRINT) ; 1476-5578 (ONLINE) |
| DOI | |
| Verlag | Basingstoke: Nature Publishing Group |
| Zusammenfassung | Ubiquitously expressed genes have been implicated in a variety of specific behaviors, including responses to ethanol. However, the mechanisms that confer this behavioral specificity have remained elusive. Previously, we showed that the ubiquitously expressed small GTPase Arf6 is required for normal ethanol-induced sedation in adult Drosophila. Here, we show that this behavioral response also requires Efa6, one of (at least) three Drosophila Arf6 guanine exchange factors. Ethanol-naive Arf6 and Efa6 mutants were sensitive to ethanol-induced sedation and lacked rapid tolerance upon re-exposure to ethanol, when compared with wild-type flies. In contrast to wild-type flies, both Arf6 and Efa6 mutants preferred alcohol-containing food without prior ethanol experience. An analysis of the human ortholog of Arf6 and orthologs of Efa6 (PSD1-4) revealed that the minor G allele of single nucleotide polymorphism (SNP) rs13265422 in PSD3, as well as a haplotype containing rs13265422, was associated with an increased frequency of drinking and binge drinking episodes in adolescents. The same haplotype was also associated with increased alcohol dependence in an independent European cohort. Unlike the ubiquitously expressed human Arf6 GTPase, PSD3 localization is restricted to the brain, particularly the prefrontal cortex (PFC). Functional magnetic resonance imaging revealed that the same PSD3 haplotype was also associated with a differential functional magnetic resonance imaging signal in the PFC during a Go/No-Go task, which engages PFC-mediated executive control. Our translational analysis, therefore, suggests that PSD3 confers regional specificity to ubiquitous Arf6 in the PFC to modulate human alcohol-drinking behaviors. |
Zitierung
Gonzalez, D., Jia, T., Pinzón, J., Acevedo, S., Ojelade, S., Xu, B., Tay, N., Desrivières, S., Hernandez, J., Banaschewski, T., Büchel, A., Bokde, A., Conrod, P., Flor, H., Frouin, V., Gallinat, J., Garavan, H., Gowland, P., Heinz, A., Ittermann, B., Lathrop, M., Martinot, J.-L., Paus, T., Smolka, M., Rhodan, A., Schumann, G., & Rothenfluh, A. (2018). The Arf6 activator Efa6/PSD3 confers regional specificity and modulates ethanol consumption in Drosophila and humans. Molecular Psychiatry, 23(3), 621–628. https://doi.org/10.1038/mp.2017.112