Show simple item record Petschner Péter Tamási Viola Ádori Csaba Kirilly Eszter Andó Rómeó Tóthfalusi László Bagdy György 2018-08-30T12:19:22Z 2018-08-30T12:19:22Z 2018
dc.identifier.citation pagination=580, 17 pages; journalVolume=19; journalIssueNumber=1; journalTitle=BMC GENOMICS;
dc.identifier.uri doi:10.1186/s12864-018-4929-x
dc.description.abstract BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used entactogenic drug known to impair cognitive functions on the long-run. Both hippocampal and frontal cortical regions have well established roles in behavior, memory formation and other cognitive tasks and damage of these regions is associated with altered behavior and cognitive functions frequently described in otherwise healthy MDMA users. Meanwhile, in post-traumatic stress disorder (PTSD) patients seem to benefit from therapeutic application of the drug, where damage in hippocampal cue extinction may play a role. The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the consequences of a single dose of MDMA (15 mg/kg) 3 weeks earlier. RESULTS: The number of differentially expressed genes in the hippocampus, frontal cortex and the dorsal raphe were 481, 155, and 15, respectively. Gene set enrichment analysis of the microarray data revealed reduced expression of 'memory' and 'cognition', 'dendrite development' and 'regulation of synaptic plasticity' gene sets in the hippocampus, parallel to the downregulation of CaMK II subunits, glutamate-, CB1 cannabinoid- and EphA4, EphA5, EphA6 receptors. Downregulated gene sets in the frontal cortex were related to protein synthesis, chromatin organization, transmembrane transport processes, while 'dendrite development', 'regulation of synaptic plasticity' and 'positive regulation of synapse assembly' gene sets were upregulated besides elevated levels of a CaMK II subunit and NMDA2B glutamate receptor. Changes in the dorsal raphe region were mild and in most cases not significant. CONCLUSION: The present data raise the possibility of new synapse formation / synaptic reorganization in the frontal cortex 3 weeks after a single neurotoxic dose of MDMA. In contrast, a prolonged depression of new neurite formation in the hippocampus is proposed by downregulations of members in long-term potentiation pathway and synaptic plasticity emphasizing the particular vulnerability of this brain region and proposing a mechanism responsible for cognitive problems in healthy individuals. At the same time, these results underpin benefits of MDMA in PTSD, where the drug may help memory extinction.
dc.relation.ispartof urn:issn:1471-2164
dc.title Gene expression analysis indicates reduced memory and cognitive functions in the hippocampus and increase in synaptic reorganization in the frontal cortex 3 weeks after MDMA administration in Dark Agouti rats.
dc.type Journal Article 2018-08-27T07:04:55Z
dc.language.rfc3066 en
dc.identifier.mtmt 3406757
dc.identifier.pubmed 30071829
dc.contributor.department SE/GYTK/Gyógyszerhatástani Intézet
dc.contributor.department SE/GYTK/GYHATAS/MTA-SE Neuropszichofarmakológiai és Neurokémiai Kutatócsoport
dc.contributor.department SE/AOK/I/Genetikai, Sejt- és Immunbiológiai Intézet
dc.contributor.department SE/GYTK/GYHATAS/NAP-A-SE Új Antidepresszív Gyógyszercélpont Kutatócsoport
dc.contributor.institution Semmelweis Egyetem
dc.mtmt.swordnote : Academy of Sciences and Semmelweis University : Program : Capacities

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