PMID- 28403881
OWN - NLM
STAT- MEDLINE
DCOM- 20171030
LR  - 20181113
IS  - 1756-6606 (Electronic)
IS  - 1756-6606 (Linking)
VI  - 10
IP  - 1
DP  - 2017 Apr 12
TI  - Glucocorticoid receptor represses brain-derived neurotrophic factor expression in 
      neuron-like cells.
PG  - 12
LID - 10.1186/s13041-017-0295-x [doi]
LID - 12
AB  - Brain-derived neurotrophic factor (BDNF) is involved in many functions such as 
      neuronal growth, survival, synaptic plasticity and memorization. Altered 
      expression levels are associated with many pathological situations such as 
      depression, epilepsy, Alzheimer's, Huntington's and Parkinson's diseases. 
      Glucocorticoid receptor (GR) is also crucial for neuron functions, via binding of 
      glucocorticoid hormones (GCs). GR actions largely overlap those of BDNF. It has 
      been proposed that GR could be a regulator of BDNF expression, however the 
      molecular mechanisms involved have not been clearly defined yet. Herein, we 
      analyzed the effect of a GC agonist dexamethasone (DEX) on BDNF expression in 
      mouse neuronal primary cultures and in the newly characterized, mouse hippocampal 
      BZ cell line established by targeted oncogenesis. Mouse Bdnf gene exhibits a 
      complex genomic structure with 8 untranslated exons (I to VIII) splicing onto one 
      common and unique coding exon IX. We found that DEX significantly downregulated 
      total BDNF mRNA expression by around 30%. Expression of the highly expressed exon 
      IV and VI containing transcripts was also reduced by DEX. The GR antagonist RU486 
      abolished this effect, which is consistent with specific GR-mediated action. 
      Transient transfection assays allowed us to define a short 275 bp region within 
      exon IV promoter responsible for GR-mediated Bdnf repression. Chromatin 
      immunoprecipitation experiments demonstrated GR recruitment onto this fragment, 
      through unidentified transcription factor tethering. Altogether, GR downregulates 
      Bdnf expression through direct binding to Bdnf regulatory sequences. These 
      findings bring new insights into the crosstalk between GR and BDNF signaling 
      pathways both playing a major role in physiology and pathology of the central 
      nervous system.
FAU - Chen, Hui
AU  - Chen H
AD  - Inserm 1185, Fac Med Paris Sud, Universite Paris-Saclay, Le Kremlin-Bicetre, 
      France.
FAU - Lombes, Marc
AU  - Lombes M
AD  - Inserm 1185, Fac Med Paris Sud, Universite Paris-Saclay, Le Kremlin-Bicetre, 
      France.
AD  - Service d'Endocrinologie et des Maladies de la Reproduction, Assistance 
      Publique-Hopitaux de Paris, Hopital de Bicetre, Le Kremlin Bicetre, F-94275, 
      France.
FAU - Le Menuet, Damien
AU  - Le Menuet D
AUID- ORCID: 0000-0002-0802-7190
AD  - Inserm 1185, Fac Med Paris Sud, Universite Paris-Saclay, Le Kremlin-Bicetre, 
      France. damien.le-menuet@u-psud.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170412
PL  - England
TA  - Mol Brain
JT  - Molecular brain
JID - 101468876
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glucocorticoids)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 7S5I7G3JQL (Dexamethasone)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Brain-Derived Neurotrophic Factor/*genetics/metabolism
MH  - Cell Line
MH  - Dexamethasone/pharmacology
MH  - *Down-Regulation/drug effects
MH  - Exons/genetics
MH  - Glucocorticoids/pharmacology
MH  - Hippocampus/metabolism
MH  - Mice
MH  - Neurons/*metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Binding/drug effects
MH  - Receptors, Glucocorticoid/*metabolism
MH  - Response Elements/genetics
PMC - PMC5389111
OTO - NOTNLM
OT  - Brain-derived neurotrophic factor
OT  - Glucocorticoid receptor
OT  - Glucocorticoids
OT  - Promoters
EDAT- 2017/04/14 06:00
MHDA- 2017/10/31 06:00
PMCR- 2017/04/12
CRDT- 2017/04/14 06:00
PHST- 2016/10/27 00:00 [received]
PHST- 2017/04/05 00:00 [accepted]
PHST- 2017/04/14 06:00 [entrez]
PHST- 2017/04/14 06:00 [pubmed]
PHST- 2017/10/31 06:00 [medline]
PHST- 2017/04/12 00:00 [pmc-release]
AID - 10.1186/s13041-017-0295-x [pii]
AID - 295 [pii]
AID - 10.1186/s13041-017-0295-x [doi]
PST - epublish
SO  - Mol Brain. 2017 Apr 12;10(1):12. doi: 10.1186/s13041-017-0295-x.