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Transcriptional changes in response to ketamine ester-analogs SN 35210 and SN 35563 in the rat brain

dc.contributor.authorJacobson, Gregory M.en_NZ
dc.contributor.authorVoss, Logan J.en_NZ
dc.contributor.authorKlockars, Anicaen_NZ
dc.contributor.authorBird, Steveen_NZ
dc.contributor.authorDimitrov, Ivoen_NZ
dc.contributor.authorDenny, William A.en_NZ
dc.contributor.authorOlszewski, Pawel K.en_NZ
dc.contributor.authorSleigh, James W.en_NZ
dc.contributor.authorHarvey, Martyn G.en_NZ
dc.date.accessioned2019-06-03T22:04:24Z
dc.date.available2019-04-11en_NZ
dc.date.available2019-06-03T22:04:24Z
dc.date.issued2019en_NZ
dc.identifier.citationJacobson, G. M., Voss, L. J., Klockars, A., Bird, S., Dimitrov, I., Denny, W. A., … Harvey, M. G. (2019). Transcriptional changes in response to ketamine ester-analogs SN 35210 and SN 35563 in the rat brain. BMC GENOMICS, 20. https://doi.org/10.1186/s12864-019-5649-6en
dc.identifier.issn1471-2164en_NZ
dc.identifier.urihttps://hdl.handle.net/10289/12585
dc.description.abstractBackground Ketamine ester analogs, SN 35210 and SN 35563, demonstrate different pharmacological profiles to ketamine in animal models. Both confer hypnosis with predictably rapid offset yet, paradoxically, SN35563 induces a prolonged anti-nociceptive state. To explore underlying mechanisms, broad transcriptome changes were measured and compared across four relevant target regions of the rat brain. Results SN 35563 produced large-scale alteration of gene expression in the Basolateral Amygdala (BLA) and Paraventricular Nucleus of the Thalamus (PVT), in excess of 10x that induced by ketamine and SN 35210. A smaller and quantitatively similar number of gene changes were observed in the Insula (INS) and Nucleus Accumbens (ACB) for all three agents. In the BLA and PVT, SN 35563 caused enrichment for gene pathways related to the function and structure of glutamatergic synapses in respect to: release of neurotransmitter, configuration of postsynaptic AMPA receptors, and the underlying cytoskeletal scaffolding and alignment. Conclusion The analgesic ketamine ester analog SN 35563 induces profound large-scale changes in gene expression in key pain-related brain regions reflecting its unique prolonged pharmacodynamic profile.
dc.format.mimetypeapplication/pdf
dc.language.isoenen_NZ
dc.publisherBMCen_NZ
dc.rights© The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
dc.subjectScience & Technologyen_NZ
dc.subjectLife Sciences & Biomedicineen_NZ
dc.subjectBiotechnology & Applied Microbiologyen_NZ
dc.subjectGenetics & Heredityen_NZ
dc.subjectKetamineen_NZ
dc.subjectAnalgesiaen_NZ
dc.subjectTranscriptomeen_NZ
dc.subjectGlutamateen_NZ
dc.subjectPotassium channelsen_NZ
dc.subjectNociceptionen_NZ
dc.subjectRECEPTOR ANTAGONISTS KETAMINEen_NZ
dc.subjectMETHYL-D-ASPARTATEen_NZ
dc.subjectPARAVENTRICULAR NUCLEUSen_NZ
dc.subjectEXPRESSIONen_NZ
dc.subjectTHALAMUSen_NZ
dc.subjectGENEen_NZ
dc.subjectPROJECTIONSen_NZ
dc.subjectNETWORKSen_NZ
dc.subjectPSD-95en_NZ
dc.subjectROLESen_NZ
dc.titleTranscriptional changes in response to ketamine ester-analogs SN 35210 and SN 35563 in the rat brainen_NZ
dc.typeJournal Article
dc.identifier.doi10.1186/s12864-019-5649-6en_NZ
dc.relation.isPartOfBMC GENOMICSen_NZ
pubs.elements-id236943
pubs.publication-statusPublisheden_NZ
pubs.volume20en_NZ
uow.identifier.article-noARTN 281


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