PMID- 25634725
OWN - NLM
STAT- MEDLINE
DCOM- 20160627
LR  - 20181113
IS  - 1559-1166 (Electronic)
IS  - 0895-8696 (Linking)
VI  - 56
IP  - 4
DP  - 2015 Aug
TI  - Differential Expression and Regulation of Brain-Derived Neurotrophic Factor 
      (BDNF) mRNA Isoforms in Brain Cells from Mecp2(308/y) Mouse Model.
PG  - 758-767
LID - 10.1007/s12031-014-0487-0 [doi]
AB  - Rett syndrome (RTT) is a severe neurodevelopmental disease caused by mutations in 
      methyl-CpG-binding protein 2 (MECP2), which encodes a transcriptional modulator 
      of many genes including BDNF. BDNF comprises nine distinct promoter regions, each 
      triggering the expression of a specific transcript. The role of this diversity of 
      transcripts remains unknown. MeCP2 being highly expressed in neurons, RTT was 
      initially considered as a neuronal disease. However, recent studies have shown 
      that MeCP2 was also expressed in astrocytes. Though several studies explored Bdnf 
      IV expression in Mecp2-deficient mice, the differential expression of Bdnf 
      isoforms in Mecp2-deficient neurons and astrocytes was never studied. By using 
      TaqMan technology and a mouse model expressing a truncated Mecp2 (Mecp2(308/y)), 
      we firstly showed in neurons that Bdnf transcripts containing exon I, IIb, IIc, 
      IV, and VI are prominently expressed, whereas in astrocytes, Bdnf transcript 
      containing exon VI is preferentially expressed, suggesting a specific regulation 
      of Bdnf expression at the cellular level. Secondly, we confirmed the repressive 
      role of Mecp2 only on the expression of Bdnf VI in neurons. Our data suggested 
      that the truncated Mecp2 protein maintains its function on Bdnf expression 
      regulation in neurons and in astrocytes. Interestingly, we observed that Bdnf 
      transcripts (I and IXA), regulated by neural activity induced by bicuculline in 
      Mecp2(308/y) neurons, were not affected by histone deacetylase inhibition. In 
      contrast, Bdnf transcripts (IIb, IIc, and VI), regulated by histone 
      deacetylation, were not affected by bicuculline treatment in wild-type and 
      Mecp2(308/y) neurons. All these results reflect the complexity of regulation of 
      Bdnf gene.
FAU - Rousseaud, Audrey
AU  - Rousseaud A
AD  - Institut Cochin, INSERM U1016, Genetique, Physiopathologie et Approches 
      Pharmacologiques des Maladies Neurodeveloppementales, Universite Paris Descartes, 
      Paris, France.
FAU - Delepine, Chloe
AU  - Delepine C
AD  - Institut Cochin, INSERM U1016, Genetique, Physiopathologie et Approches 
      Pharmacologiques des Maladies Neurodeveloppementales, Universite Paris Descartes, 
      Paris, France.
FAU - Nectoux, Juliette
AU  - Nectoux J
AD  - Institut Cochin, INSERM U1016, Genetique, Physiopathologie et Approches 
      Pharmacologiques des Maladies Neurodeveloppementales, Universite Paris Descartes, 
      Paris, France.
AD  - Laboratoire de Biochimie et Genetique Moleculaire, Assistance Publique - Hopitaux 
      de Paris, GHU Cochin-Broca-Hotel Dieu, Paris, France.
FAU - Billuart, Pierre
AU  - Billuart P
AD  - Institut Cochin, INSERM U1016, Genetique, Physiopathologie et Approches 
      Pharmacologiques des Maladies Neurodeveloppementales, Universite Paris Descartes, 
      Paris, France.
FAU - Bienvenu, Thierry
AU  - Bienvenu T
AD  - Institut Cochin, INSERM U1016, Genetique, Physiopathologie et Approches 
      Pharmacologiques des Maladies Neurodeveloppementales, Universite Paris Descartes, 
      Paris, France. thierry.bienvenu@inserm.fr.
AD  - Laboratoire de Biochimie et Genetique Moleculaire, Assistance Publique - Hopitaux 
      de Paris, GHU Cochin-Broca-Hotel Dieu, Paris, France. thierry.bienvenu@inserm.fr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150130
PL  - United States
TA  - J Mol Neurosci
JT  - Journal of molecular neuroscience : MN
JID - 9002991
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Mecp2 protein, mouse)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Animals
MH  - Astrocytes/metabolism
MH  - Brain/cytology/*metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cells, Cultured
MH  - Exons
MH  - Methyl-CpG-Binding Protein 2/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neurons/metabolism
MH  - Protein Isoforms/genetics/metabolism
MH  - RNA, Messenger/genetics/metabolism
EDAT- 2015/01/31 06:00
MHDA- 2016/06/28 06:00
CRDT- 2015/01/31 06:00
PHST- 2014/10/09 00:00 [received]
PHST- 2014/12/25 00:00 [accepted]
PHST- 2015/01/31 06:00 [entrez]
PHST- 2015/01/31 06:00 [pubmed]
PHST- 2016/06/28 06:00 [medline]
AID - 10.1007/s12031-014-0487-0 [pii]
AID - 10.1007/s12031-014-0487-0 [doi]
PST - ppublish
SO  - J Mol Neurosci. 2015 Aug;56(4):758-767. doi: 10.1007/s12031-014-0487-0. Epub 2015 
      Jan 30.