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dc.contributor.authorBeiersdorf, Johannes
dc.contributor.authorHevesi, Zsofia
dc.contributor.authorCalvigioni, Daniela
dc.contributor.authorPyszkowski, Jakob
dc.contributor.authorRomanov, Roman
dc.contributor.authorSzodorai, Edit
dc.contributor.authorLubec, Gert
dc.contributor.authorShirran, Sally
dc.contributor.authorBotting, Catherine H.
dc.contributor.authorKasper, Siegfried
dc.contributor.authorGuy, Geoffrey W.
dc.contributor.authorGray, Roy
dc.contributor.authorDi Marzo, Vincenzo
dc.contributor.authorHarkany, Tibor
dc.contributor.authorKeimpema, Erik
dc.date.accessioned2020-12-16T16:30:19Z
dc.date.available2020-12-16T16:30:19Z
dc.date.issued2020-12-03
dc.identifier.citationBeiersdorf , J , Hevesi , Z , Calvigioni , D , Pyszkowski , J , Romanov , R , Szodorai , E , Lubec , G , Shirran , S , Botting , C H , Kasper , S , Guy , G W , Gray , R , Di Marzo , V , Harkany , T & Keimpema , E 2020 , ' Adverse effects of Δ 9 -tetrahydrocannabinol on neuronal bioenergetics during postnatal development ' , JCI Insight , vol. 5 , no. 23 , e135418 . https://doi.org/10.1172/jci.insight.135418en
dc.identifier.issn2379-3708
dc.identifier.otherPURE: 271709030
dc.identifier.otherPURE UUID: e7931f07-0f08-4d2e-8fc1-630b971ac1f9
dc.identifier.otherScopus: 85097211176
dc.identifier.otherPubMed: 33141759
dc.identifier.otherORCID: /0000-0003-3516-3507/work/85562882
dc.identifier.otherWOS: 000597060000001
dc.identifier.urihttp://hdl.handle.net/10023/21165
dc.descriptionThis work was supported by a grant from FWF (P 34121-B; EK), GW Pharmaceuticals, as well as funding from the Swedish Research Council (2018-02838; TH), the European Research Council (SECRET-CELLS, ERC-2015-AdG-695136; TH), and the Wellcome Trust (grant no. 094476/Z/10/Z, which funded the purchase of the TripleTOF 5600 mass spectrometer at the BSRC Mass Spectrometry and Proteomics Facility, University of St. Andrews).en
dc.description.abstractOngoing societal changes in views on the medical and recreational roles of cannabis increased the use of concentrated plant extracts with a Δ9-tetrahydrocannabinol (THC) content of more than 90%. Even though prenatal THC exposure is widely considered adverse for neuronal development, equivalent experimental data for young age cohorts are largely lacking. Here, we administered plant-derived THC (1 or 5 mg/kg) to mice daily during P5–P16 and P5–P35 and monitored its effects on hippocampal neuronal survival and specification by high-resolution imaging and iTRAQ proteomics, respectively. We found that THC indiscriminately affects pyramidal cells and both cannabinoid receptor 1+ (CB1R)+ and CB1R– interneurons by P16. THC particularly disrupted the expression of mitochondrial proteins (complexes I–IV), a change that had persisted even 4 months after the end of drug exposure. This was reflected by a THC-induced loss of membrane integrity occluding mitochondrial respiration and could be partially or completely rescued by pH stabilization, antioxidants, bypassed glycolysis, and targeting either mitochondrial soluble adenylyl cyclase or the mitochondrial voltage-dependent anion channel. Overall, THC exposure during infancy induces significant and long-lasting reorganization of neuronal circuits through mechanisms that, in large part, render cellular bioenergetics insufficient to sustain key developmental processes in otherwise healthy neurons.
dc.format.extent20
dc.language.isoeng
dc.relation.ispartofJCI Insighten
dc.rightsCopyright: © 2020, Beiersdorf et al. This is an open access article published under the terms of the Creative Commons Attribution 4.0 International License.en
dc.subjectQD Chemistryen
dc.subjectQH301 Biologyen
dc.subjectMedicine(all)en
dc.subjectNDASen
dc.subject.lccQDen
dc.subject.lccQH301en
dc.titleAdverse effects of Δ9-tetrahydrocannabinol on neuronal bioenergetics during postnatal developmenten
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Chemistryen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.1172/jci.insight.135418
dc.description.statusPeer revieweden


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