PMID- 28830794
OWN - NLM
STAT- MEDLINE
DCOM- 20190122
LR  - 20210109
IS  - 1878-4216 (Electronic)
IS  - 0278-5846 (Print)
IS  - 0278-5846 (Linking)
VI  - 82
DP  - 2018 Mar 2
TI  - Regulation of gene transcription in bipolar disorders: Role of DNA methylation in 
      the relationship between prodynorphin and brain derived neurotrophic factor.
PG  - 314-321
LID - S0278-5846(17)30480-3 [pii]
LID - 10.1016/j.pnpbp.2017.08.011 [doi]
AB  - Bipolar Disorder (BD) is a prevalent and disabling condition, determined by 
      gene-environment interactions, possibly mediated by epigenetic mechanisms. The 
      present study aimed at investigating the transcriptional regulation of BD 
      selected target genes by DNA methylation in peripheral blood mononuclear cells of 
      patients with a DSM-5 diagnosis of type I (BD-I) and type II (BD-II) Bipolar 
      Disorders (n=99), as well as of healthy controls (CT, n=42). The analysis of gene 
      expression revealed prodynorphin (PDYN) mRNA levels significantly reduced in 
      subjects with BD-II but not in those with BD-I, when compared to CT. Other target 
      genes (i.e. catechol-O-methyltransferase (COMT), glutamate decarboxylase (GAD67), 
      serotonin transporter (SERT) mRNA levels remained unaltered. Consistently, an 
      increase in DNA methylation at PDYN gene promoter was observed in BD-II patients 
      vs CT. After stratifying data on the basis of pharmacotherapy, patients on 
      mood-stabilizers (i.e., lithium and anticonvulsants) were found to have lower DNA 
      methylation at PDYN gene promoter. A significantly positive correlation in 
      promoter DNA methylation was observed in all subjects between PDYN and brain 
      derived neurotrophic factor (BDNF), whose methylation status had been previously 
      found altered in BD. Moreover, among key genes relevant for DNA methylation 
      establishment here analysed, an up-regulation of DNA Methyl Transferases 3b 
      (DNMT3b) and of the methyl binding protein MeCP2 (methyl CpG binding protein 2) 
      mRNA levels was also observed again just in BD-II subjects. A clear selective 
      role of DNA methylation involvement in BD-II is shown here, further supporting a 
      role for BDNF and its possible interaction with PDYN. These data might be 
      relevant in the pathophysiology of BD, both in relation to BDNF and for the 
      improvement of available treatments and development of novel ones that modulate 
      epigenetic signatures.
CI  - Copyright (c) 2017 Elsevier Inc. All rights reserved.
FAU - D'Addario, Claudio
AU  - D'Addario C
AD  - Faculty of Bioscience and Technology for Food, Agriculture and Environment, 
      University of Teramo, Italy; Department of Clinical Neuroscience, Karolinska 
      Institute, Stockholm, Sweden. Electronic address: cdaddario@unite.it.
FAU - Palazzo, Maria Carlotta
AU  - Palazzo MC
AD  - Centro Sant'Ambrogio Ordine Ospedaliero San Giovanni di Dio Fatebenefratelli, 
      Milano, Italy.
FAU - Benatti, Beatrice
AU  - Benatti B
AD  - Department of Psychiatry, Universita degli Studi di Milano, Fondazione IRRCS Ca' 
      Granda, Ospedale Maggiore Policlinico, Milano, Italy.
FAU - Grancini, Benedetta
AU  - Grancini B
AD  - Department of Psychiatry, Universita degli Studi di Milano, Fondazione IRRCS Ca' 
      Granda, Ospedale Maggiore Policlinico, Milano, Italy.
FAU - Pucci, Mariangela
AU  - Pucci M
AD  - Faculty of Bioscience and Technology for Food, Agriculture and Environment, 
      University of Teramo, Italy.
FAU - Di Francesco, Andrea
AU  - Di Francesco A
AD  - Experimental Gerontology Section, Translational Gerontology Branch, National 
      Institute on Aging, Baltimore, MD, USA.
FAU - Camuri, Giulia
AU  - Camuri G
AD  - Department of Psychiatry, Universita degli Studi di Milano, Fondazione IRRCS Ca' 
      Granda, Ospedale Maggiore Policlinico, Milano, Italy.
FAU - Galimberti, Daniela
AU  - Galimberti D
AD  - Department of Neurology, Universita degli Studi di Milano, Fondazione IRRCS Ca' 
      Granda, Ospedale Maggiore Policlinico, Milano, Italy.
FAU - Fenoglio, Chiara
AU  - Fenoglio C
AD  - Department of Neurology, Universita degli Studi di Milano, Fondazione IRRCS Ca' 
      Granda, Ospedale Maggiore Policlinico, Milano, Italy.
FAU - Scarpini, Elio
AU  - Scarpini E
AD  - Department of Neurology, Universita degli Studi di Milano, Fondazione IRRCS Ca' 
      Granda, Ospedale Maggiore Policlinico, Milano, Italy.
FAU - Altamura, A Carlo
AU  - Altamura AC
AD  - Department of Psychiatry, Universita degli Studi di Milano, Fondazione IRRCS Ca' 
      Granda, Ospedale Maggiore Policlinico, Milano, Italy.
FAU - Maccarrone, Mauro
AU  - Maccarrone M
AD  - Department of Medicine, Campus Bio-Medico University of Rome, Rome, Italy; 
      European Center for Brain Research, IRCCS Santa Lucia Foundation, Rome, Italy.
FAU - Dell'Osso, Bernardo
AU  - Dell'Osso B
AD  - Department of Psychiatry, Universita degli Studi di Milano, Fondazione IRRCS Ca' 
      Granda, Ospedale Maggiore Policlinico, Milano, Italy; Department of Psychiatry 
      and Behavioral Sciences, Bipolar Disorders Clinic, Stanford University, CA, USA. 
      Electronic address: bernardo.dellosso@unimi.it.
LA  - eng
GR  - Z01 AG000362/ImNIH/Intramural NIH HHS/United States
GR  - Z99 AG999999/ImNIH/Intramural NIH HHS/United States
GR  - ZIA AG000362-02/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20170819
PL  - England
TA  - Prog Neuropsychopharmacol Biol Psychiatry
JT  - Progress in neuro-psychopharmacology & biological psychiatry
JID - 8211617
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Enkephalins)
RN  - 0 (Protein Precursors)
RN  - 0 (RNA, Messenger)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - 93443-35-7 (preproenkephalin)
SB  - IM
MH  - Aged
MH  - Bipolar Disorder/drug therapy/genetics/*metabolism
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - *DNA Methylation
MH  - Enkephalins/*metabolism
MH  - Epigenesis, Genetic
MH  - Female
MH  - *Gene Expression Regulation/physiology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Promoter Regions, Genetic
MH  - Protein Precursors/*metabolism
MH  - RNA, Messenger/metabolism
MH  - *Transcription, Genetic/physiology
PMC - PMC5859566
MID - NIHMS947612
OTO - NOTNLM
OT  - Bipolar disorder
OT  - Brain derived neurotrophic factor
OT  - DNA methylation
OT  - Epigenetics
OT  - Prodynorphin
COIS- Statement of interest MCP, BB, GC, ADF, MP, CD, MM declare to have nothing to 
      disclose.
EDAT- 2017/08/24 06:00
MHDA- 2019/01/23 06:00
PMCR- 2018/04/02
CRDT- 2017/08/24 06:00
PHST- 2017/06/21 00:00 [received]
PHST- 2017/08/04 00:00 [revised]
PHST- 2017/08/13 00:00 [accepted]
PHST- 2017/08/24 06:00 [pubmed]
PHST- 2019/01/23 06:00 [medline]
PHST- 2017/08/24 06:00 [entrez]
PHST- 2018/04/02 00:00 [pmc-release]
AID - S0278-5846(17)30480-3 [pii]
AID - 10.1016/j.pnpbp.2017.08.011 [doi]
PST - ppublish
SO  - Prog Neuropsychopharmacol Biol Psychiatry. 2018 Mar 2;82:314-321. doi: 
      10.1016/j.pnpbp.2017.08.011. Epub 2017 Aug 19.