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
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...
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| Format: | Article |
| Language: | English |
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BMC
2018-08-01
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| Series: | BMC Genomics |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12864-018-4929-x |
| _version_ | 1818971009764556800 |
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| author | Peter Petschner Viola Tamasi Csaba Adori Eszter Kirilly Romeo D. Ando Laszlo Tothfalusi Gyorgy Bagdy |
| author_facet | Peter Petschner Viola Tamasi Csaba Adori Eszter Kirilly Romeo D. Ando Laszlo Tothfalusi Gyorgy Bagdy |
| author_sort | Peter Petschner |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-20T14:45:34Z |
| format | Article |
| id | doaj.art-5f7eddae31ea483baee5f813c66d783a |
| institution | Directory Open Access Journal |
| issn | 1471-2164 |
| language | English |
| last_indexed | 2024-12-20T14:45:34Z |
| publishDate | 2018-08-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj.art-5f7eddae31ea483baee5f813c66d783a2022-12-21T19:37:08ZengBMCBMC Genomics1471-21642018-08-0119111710.1186/s12864-018-4929-xGene 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 ratsPeter Petschner0Viola Tamasi1Csaba Adori2Eszter Kirilly3Romeo D. Ando4Laszlo Tothfalusi5Gyorgy Bagdy6Department of Pharmacodynamics, Semmelweis UniversityDepartment of Genetics, Cell- and Immunobiology, Semmelweis UniversityDepartment of Pharmacodynamics, Semmelweis UniversityDepartment of Pharmacodynamics, Semmelweis UniversityDepartment of Pharmacodynamics, Semmelweis UniversityDepartment of Pharmacodynamics, Semmelweis UniversityDepartment of Pharmacodynamics, Semmelweis UniversityAbstract 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.http://link.springer.com/article/10.1186/s12864-018-4929-xEcstasyEndocannabinoidCB1RhoGTPaseSerotoninGene expression |
| spellingShingle | Peter Petschner Viola Tamasi Csaba Adori Eszter Kirilly Romeo D. Ando Laszlo Tothfalusi Gyorgy Bagdy 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 BMC Genomics Ecstasy Endocannabinoid CB1 RhoGTPase Serotonin Gene expression |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Ecstasy Endocannabinoid CB1 RhoGTPase Serotonin Gene expression |
| url | http://link.springer.com/article/10.1186/s12864-018-4929-x |
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