PMID- 28444170
OWN - NLM
STAT- MEDLINE
DCOM- 20180501
LR  - 20220409
IS  - 1460-2199 (Electronic)
IS  - 1047-3211 (Linking)
VI  - 27
IP  - 8
DP  - 2017 Aug 1
TI  - Neuronal Activity, TGFbeta-Signaling and Unpredictable Chronic Stress Modulate 
      Transcription of Gadd45 Family Members and DNA Methylation in the Hippocampus.
PG  - 4166-4181
LID - 10.1093/cercor/bhx095 [doi]
AB  - Neuronal activity is altered in several neurological and psychiatric diseases. 
      Upon depolarization not only neurotransmitters are released but also cytokines 
      and other activators of signaling cascades. Unraveling their complex implication 
      in transcriptional control in receiving cells will contribute to understand 
      specific central nervous system (CNS) pathologies and will be of therapeutically 
      interest. In this study we depolarized mature hippocampal neurons in vitro using 
      KCl and revealed increased release not only of brain-derived neurotrophic factor 
      (BDNF) but also of transforming growth factor beta (TGFB). Neuronal activity 
      together with BDNF and TGFB controls transcription of DNA modifying enzymes 
      specifically members of the DNA-damage-inducible (Gadd) family, Gadd45a, Gadd45b, 
      and Gadd45g. MeDIP followed by massive parallel sequencing and transcriptome 
      analyses revealed less DNA methylation upon KCl treatment. Psychiatric 
      disorder-related genes, namely Tshz1, Foxn3, Jarid2, Per1, Map3k5, and Arc are 
      transcriptionally activated and demethylated upon neuronal activation. To analyze 
      whether misexpression of Gadd45 family members are associated with psychiatric 
      diseases, we applied unpredictable chronic mild stress (UCMS) as established 
      model for depression to mice. UCMS led to reduced expression of Gadd45 family 
      members. Taken together, our data demonstrate that Gadd45 family members are new 
      putative targets for UCMS treatments.
CI  - (c) The Author 2017. Published by Oxford University Press.
FAU - Grassi, Daniela
AU  - Grassi D
AD  - Department of Molecular Embryology, Institute of Anatomy and Cell Biology, 
      Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
AD  - Department of Basic Biomedical Sciences, Faculty of Biomedical Science and 
      Health, Universidad Europea de Madrid, Madrid, Spain.
FAU - Franz, Henriette
AU  - Franz H
AD  - Department of Molecular Embryology, Institute of Anatomy and Cell Biology, 
      Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
FAU - Vezzali, Riccardo
AU  - Vezzali R
AD  - Department of Molecular Embryology, Institute of Anatomy and Cell Biology, 
      Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
FAU - Bovio, Patrick
AU  - Bovio P
AD  - Department of Molecular Embryology, Institute of Anatomy and Cell Biology, 
      Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
AD  - Faculty of Biology, University of Freiburg, 79104 Freiburg, Germany.
FAU - Heidrich, Stefanie
AU  - Heidrich S
AD  - Department of Molecular Embryology, Institute of Anatomy and Cell Biology, 
      Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
FAU - Dehghanian, Fariba
AU  - Dehghanian F
AD  - Department of Molecular Embryology, Institute of Anatomy and Cell Biology, 
      Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
FAU - Lagunas, Natalia
AU  - Lagunas N
AD  - Inserm U 930, Universite Francois Rabelais, 37200 Tours, France.
FAU - Belzung, Catherine
AU  - Belzung C
AD  - Inserm U 930, Universite Francois Rabelais, 37200 Tours, France.
FAU - Krieglstein, Kerstin
AU  - Krieglstein K
AD  - Department of Molecular Embryology, Institute of Anatomy and Cell Biology, 
      Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
AD  - BIOSS Centre for Biological Signalling Studies, University of Freiburg, 79104 
      Freiburg, Germany.
FAU - Vogel, Tanja
AU  - Vogel T
AD  - Department of Molecular Embryology, Institute of Anatomy and Cell Biology, 
      Faculty of Medicine, University of Freiburg, 79104 Freiburg, Germany.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cereb Cortex
JT  - Cerebral cortex (New York, N.Y. : 1991)
JID - 9110718
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Gadd45a protein, mouse)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type I)
SB  - IM
MH  - Animals
MH  - Autistic Disorder/genetics/metabolism
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - Cell Cycle Proteins/*metabolism
MH  - Cells, Cultured
MH  - Chronic Disease
MH  - *DNA Methylation
MH  - Depressive Disorder/genetics/metabolism
MH  - Disease Models, Animal
MH  - Hippocampus/*metabolism
MH  - Male
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Neurons/*metabolism
MH  - Nuclear Proteins/*metabolism
MH  - Protein Serine-Threonine Kinases/metabolism
MH  - Receptor, Transforming Growth Factor-beta Type I
MH  - Receptors, Transforming Growth Factor beta/metabolism
MH  - Signal Transduction
MH  - Stress, Psychological/genetics/*metabolism
MH  - Synaptic Transmission/physiology
MH  - Transcriptome
MH  - Transforming Growth Factor beta/*metabolism
OTO - NOTNLM
OT  - ARC
OT  - BDNF
OT  - DNA demethylation
OT  - depolarization
OT  - depression
EDAT- 2017/04/27 06:00
MHDA- 2018/05/02 06:00
CRDT- 2017/04/27 06:00
PHST- 2016/11/30 00:00 [received]
PHST- 2017/04/04 00:00 [accepted]
PHST- 2017/04/27 06:00 [pubmed]
PHST- 2018/05/02 06:00 [medline]
PHST- 2017/04/27 06:00 [entrez]
AID - 3746073 [pii]
AID - 10.1093/cercor/bhx095 [doi]
PST - ppublish
SO  - Cereb Cortex. 2017 Aug 1;27(8):4166-4181. doi: 10.1093/cercor/bhx095.