PMID- 30559663
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200929
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 9
DP  - 2018
TI  - Downregulation of the Vitamin D Receptor Regulated Gene Set in the Hippocampus 
      After MDMA Treatment.
PG  - 1373
LID - 10.3389/fphar.2018.01373 [doi]
LID - 1373
AB  - 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.
FAU - Petschner, Peter
AU  - Petschner P
AD  - Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
AD  - MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian 
      Academy of Sciences, Semmelweis University, Budapest, Hungary.
FAU - Balogh, Noemi
AU  - Balogh N
AD  - Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
FAU - Adori, Csaba
AU  - Adori C
AD  - Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
FAU - Tamasi, Viola
AU  - Tamasi V
AD  - Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, 
      Hungary.
FAU - Kumar, Sahel
AU  - Kumar S
AD  - Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
FAU - Juhasz, Gabriella
AU  - Juhasz G
AD  - Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
AD  - SE-NAP 2 Genetic Brain Imaging Migraine Research Group, Hungarian Brain Research 
      Program, Semmelweis University, Budapest, Hungary.
AD  - NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research 
      Program, Semmelweis University, Budapest, Hungary.
FAU - Bagdy, Gyorgy
AU  - Bagdy G
AD  - Department of Pharmacodynamics, Semmelweis University, Budapest, Hungary.
AD  - MTA-SE Neuropsychopharmacology and Neurochemistry Research Group, Hungarian 
      Academy of Sciences, Semmelweis University, Budapest, Hungary.
AD  - NAP-2-SE New Antidepressant Target Research Group, Hungarian Brain Research 
      Program, Semmelweis University, Budapest, Hungary.
LA  - eng
PT  - Journal Article
DEP - 20181203
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6287013
OTO - NOTNLM
OT  - ecstasy
OT  - gene expression
OT  - hippocampus
OT  - long-term potentiation
OT  - microarray
OT  - vitamin D
EDAT- 2018/12/19 06:00
MHDA- 2018/12/19 06:01
PMCR- 2018/12/03
CRDT- 2018/12/19 06:00
PHST- 2018/09/13 00:00 [received]
PHST- 2018/11/08 00:00 [accepted]
PHST- 2018/12/19 06:00 [entrez]
PHST- 2018/12/19 06:00 [pubmed]
PHST- 2018/12/19 06:01 [medline]
PHST- 2018/12/03 00:00 [pmc-release]
AID - 10.3389/fphar.2018.01373 [doi]
PST - epublish
SO  - Front Pharmacol. 2018 Dec 3;9:1373. doi: 10.3389/fphar.2018.01373. eCollection 
      2018.