Downregulation of the Vitamin D Receptor Regulated Gene Set in the Hippocampus After MDMA Treatment.
Peter Petschner, Noemi Balogh, Csaba Ádori, Viola Tamasi, Sahel Kumar, Gabriella Juhasz, György Bagdy
Frontiers in Pharmacology 2018 DOI: 10.3389/fphar.2018.01373 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational animal study Peer reviewed |
|---|---|
| Population | Dark Agouti rats |
| Intervention | MDMA |
| Dose | 15 mg/kg |
| Duration | Three weeks after injection |
| Measures | Illumina whole-genome beadarrays, gene-set enrichment analysis (GSEA), MSigDB transcription factor sets |
| Topics | MDMA |
| Keywords | Gene expression Hippocampus Long-term potentiation Microarray Vitamin d |
| Key findings | Three weeks after a single 15 mg/kg intraperitoneal MDMA injection, rat hippocampal gene expression showed 13 downregulated and one upregulated transcription factor gene sets, including vitamin D receptor, FoxO, and Pax4 sets. The authors argue that the predominance of ischemia-related transcription factors indicates hypoxia/ischemia occurs in the hippocampus after MDMA and may underlie its selective vulnerability, and suggest vitamin D supplementation as a possible protective strategy. |
Abstract
The active ingredient of ecstasy, ±3,4-methylenedioxymethamphetamine (MDMA), in addition to its initial reinforcing effects, induces selective and non-selective brain damage. Evidences suggest that the hippocampus (HC), a central region for cognition, may be especially vulnerable to impairments on the long-run, nevertheless, transcription factors that may precede and regulate such chronic changes remained uninvestigated in this region. In the current study, we used gene-set enrichment analysis (GSEA) to reveal possible transcription factor candidates responsible for enhanced vulnerability of HC after MDMA administration. Dark Agouti rats were intraperitoneally injected with saline or 15 mg/kg MDMA. Three weeks later HC gene expression was measured by Illumina whole-genome beadarrays and GSEA was performed with MSigDB transcription factor sets. The number of significantly altered genes on the genome level (significance < 0.001) in up/downregulated sets was also counted. MDMA upregulated one, and downregulated 13 gene sets in the HC of rats, compared to controls, including Pax4, Pitx2, FoxJ2, FoxO1, Oct1, Sp3, AP3, FoxO4, and vitamin D receptor (VDR)-regulated sets (q-value <0.05). VDR-regulated set contained the second highest number of significantly altered genes, including among others, Camk2n2, Gria3, and Grin2a. Most identified transcription factors are implicated in the response to ischemia confirming that serious hypoxia/ischemia occurs in the HC after MDMA administration, which may contribute to the selective vulnerability of this brain region. Moreover, our results also raise the possibility that vitamin D supplementation, in addition to the commonly used antioxidants, could be a potential alternative method to attenuate MDMA-induced chronic hippocampal impairments.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cites 13
- Damage of serotonergic axons and immunolocalization of Hsp27, Hsp72, and Hsp90 molecular chaperones after a single dose of MDMA administration in Dark Agouti rat: Temporal, spatial, and cellular patterns The Journal of Comparative Neurology 2006
- Preliminary evidence of hippocampal damage in chronic users of ecstasy Journal of Neurology, Neurosurgery, and Psychiatry March 28, 2011
- Acute and long-term effects of a single dose of MDMA on aggression in Dark Agouti rats The International Journal of Neuropsychopharmacology August 1, 2005
- The Acute Effect in Rats of 3, 4‐Methylenedioxyethamphetamine (MDEA, “Eve”) on Body Temperature and Long Term Degeneration of 5‐HT Neurones in Brain: A Comparison with MDMA (“Ecstasy”) Pharmacology & Toxicology June 1, 1999
- Human Metabolome Changes after a Single Dose of 3,4-Methylenedioxymethamphetamine (MDMA) with Special Focus on Steroid Metabolism and Inflammation Processes Journal of Proteome Research June 27, 2018
and 8 more in the library