Differential gene expression in the mesocorticolimbic system of innately high- and low-impulsive rats

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dc.contributor.authorMoloney, Gerard M.
dc.contributor.authorvan Oeffelen, Wesley E. P. A.
dc.contributor.authorRyan, Feargal J.
dc.contributor.authorvan de Wouw, Marcel
dc.contributor.authorCowan, Caitlin S. M.
dc.contributor.authorClaesson, Marcus J.
dc.contributor.authorSchellekens, Harriët
dc.contributor.authorDinan, Timothy G.
dc.contributor.authorCryan, John F.
dc.contributor.funderEuropean Regional Development Funden
dc.contributor.funderEnterprise Irelanden
dc.contributor.funderHigher Education Authorityen
dc.contributor.funderSeventh Framework Programmeen
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderHorizon 2020en
dc.contributor.funderH2020 Marie Skłodowska-Curie Actionsen
dc.date.accessioned2019-04-15T12:43:51Z
dc.date.available2019-04-15T12:43:51Z
dc.date.issued2019-02-06
dc.date.updated2019-04-15T12:30:39Z
dc.description.abstractImpulsivity is an important component of many psychiatric illnesses and has been associated with a number of psychiatric disorders such as bipolar disorder and attention deficit / hyperactivity disorder (ADHD). Exploring the different aspects of impulsive behaviour and assigning these to specific neurobiological pathways would advance our interpretation of disorders for which impulsivity is key. Pharmacological studies have implicated a number of neurotransmitters in impulsivity, which in turn have been shown to be affected by several genes in both rodent and human studies of impulsivity. Here, we examine impulsivity-related differences in gene expression in finer detail, using the 2-choice serial reaction time task (2-CSRTT) to assess the molecular signature of impulsivity in brain regions previously linked to impulsive behaviour. Wistar rats were rated as high, (n = 6), intermediate, (n = 12) or low impulsive (n = 6), based on premature responses in the 2-CSRTT, after which RNA was extracted from the nucleus accumbens core (NAcc) and ventral prefrontal cortex (vPFC). RNA from the NAcc and vPFC of high and low impulsivity rats (n = 6 per group) was analysed for differential gene expression patterns and exon usage using RNA poly-A tail sequencing. Pnisr, Mal, and Tspan2 were significantly increased in the NAcc of highly impulsive rats, whereas Ube3a was significantly decreased. No differences were seen in the vPFC. In addition to changes in gene expression, Tspan2 displayed differential exon usage in impulsive rats, while functionally, gene expression changes were related to membrane depolarisation and changes in exon usage were linked to sphingolipid breakdown. The changes in gene expression and exon usage observed in this study represent an important step towards defining the molecular architecture of impulsivity. This study therefore represents an important starting point for analysis of the biological role of impulsivity in addiction and other neurological conditions associated with impulsive phenotypes.en
dc.description.sponsorshipHigher Education Authority (Molecular Medicine Ireland (as part of the Clinical & Translational Research Scholars Programme under the Programme for Research in Third Level Institutions (PRTLI) Cycle 5 and co-funded under the European Regional Development Fund (ERDF)); Enterprise Ireland (Grant Numbers CC2008-001 and TC2013-000);en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMoloney, G. M., van Oeffelen, W. E. P. A., Ryan, F. J., van de Wouw, M., Cowan, C., Claesson, M. J., Schellekens, H., Dinan, T. G. and Cryan, J. F. (2019) 'Differential gene expression in the mesocorticolimbic system of innately high- and low-impulsive rats', Behavioural Brain Research, 364, pp. 193-204. doi: 10.1016/j.bbr.2019.01.022en
dc.identifier.doi10.1016/j.bbr.2019.01.022en
dc.identifier.eissn1872-7549
dc.identifier.endpage204en
dc.identifier.issn0166-4328
dc.identifier.journaltitleBehavioural Brain Researchen
dc.identifier.startpage193en
dc.identifier.urihttps://hdl.handle.net/10468/7764
dc.identifier.volume364en
dc.language.isoenen
dc.publisherElsevieren
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP1::HEALTH/278948/EU/Translational Adolescent and Childhood Therapeutic Interventions in Compulsive Syndromes/TACTICSen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.relation.projectinfo:eu-repo/grantAgreement/EC/H2020::MSCA-IF-EF-ST/797592/EU/Gut microbiota-Microglia Interactions in NeuroDevelopment/GutMINDen
dc.relation.urihttp://www.sciencedirect.com/science/article/pii/S0166432818308714
dc.rights© 2019 Elsevier B.V. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 licenseen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectImpulsivityen
dc.subjectNucleus accumbens coreen
dc.subjectRNA-sequencingen
dc.subjectGenomicsen
dc.subjectVentral Prefrontal cortexen
dc.titleDifferential gene expression in the mesocorticolimbic system of innately high- and low-impulsive ratsen
dc.typeArticle (peer-reviewed)en
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