PMID- 23027959
OWN - NLM
STAT- MEDLINE
DCOM- 20121231
LR  - 20211021
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 109
IP  - 42
DP  - 2012 Oct 16
TI  - Activity-dependent BDNF release and TRPC signaling is impaired in hippocampal 
      neurons of Mecp2 mutant mice.
PG  - 17087-92
LID - 10.1073/pnas.1205271109 [doi]
AB  - Dysfunction of the neurotrophin brain-derived neurotrophic factor (BDNF) is 
      implicated in Rett syndrome (RTT), but the state of its releasable pool and 
      downstream signaling in mice lacking methyl-CpG-binding protein-2 (Mecp2) is 
      unknown. Here, we show that membrane currents and dendritic Ca(2+) signals evoked 
      by recombinant BDNF or an activator of diacylglycerol (DAG)-sensitive transient 
      receptor potential canonical (TRPC) channels are impaired in CA3 pyramidal 
      neurons of symptomatic Mecp2 mutant mice. TRPC3 and TRPC6 mRNA and protein levels 
      are lower in Mecp2 mutant hippocampus, and chromatin immunoprecipitation (ChIP) 
      identified Trpc3 as a target of MeCP2 transcriptional regulation. BDNF mRNA and 
      protein levels are also lower in Mecp2 mutant hippocampus and dentate gyrus 
      granule cells, which is reflected in impaired activity-dependent release of 
      endogenous BDNF estimated from TRPC currents and dendritic Ca(2+) signals in CA3 
      pyramidal neurons. These results identify the gene encoding TRPC3 channels as a 
      MeCP2 target and suggest a potential therapeutic strategy to boost impaired BDNF 
      signaling in RTT.
FAU - Li, Wei
AU  - Li W
AD  - Department of Neurobiology, Civitan International Research Center, The University 
      of Alabama at Birmingham, Birmingham, AL 35294, USA.
FAU - Calfa, Gaston
AU  - Calfa G
FAU - Larimore, Jennifer
AU  - Larimore J
FAU - Pozzo-Miller, Lucas
AU  - Pozzo-Miller L
LA  - eng
GR  - P30 NS047466/NS/NINDS NIH HHS/United States
GR  - P30 HD038985/HD/NICHD NIH HHS/United States
GR  - R01 NS040593/NS/NINDS NIH HHS/United States
GR  - R01 NS065027/NS/NINDS NIH HHS/United States
GR  - P30-HD38985/HD/NICHD NIH HHS/United States
GR  - NS-065027/NS/NINDS NIH HHS/United States
GR  - P30-NS47466/NS/NINDS NIH HHS/United States
GR  - P30-NS57098/NS/NINDS NIH HHS/United States
GR  - P30 NS057098/NS/NINDS NIH HHS/United States
GR  - NS-40593/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20121001
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Mecp2 protein, mouse)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (TRPC Cation Channels)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Hippocampus/*cytology
MH  - Immunohistochemistry
MH  - Methyl-CpG-Binding Protein 2/*genetics
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Microscopy, Confocal
MH  - Patch-Clamp Techniques
MH  - Pyramidal Cells/*physiology
MH  - Real-Time Polymerase Chain Reaction
MH  - Rett Syndrome/genetics/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction/*physiology
MH  - TRPC Cation Channels/*metabolism
PMC - PMC3479462
COIS- The authors declare no conflict of interest.
EDAT- 2012/10/03 06:00
MHDA- 2013/01/01 06:00
PMCR- 2013/04/16
CRDT- 2012/10/03 06:00
PHST- 2012/10/03 06:00 [entrez]
PHST- 2012/10/03 06:00 [pubmed]
PHST- 2013/01/01 06:00 [medline]
PHST- 2013/04/16 00:00 [pmc-release]
AID - 1205271109 [pii]
AID - 201205271 [pii]
AID - 10.1073/pnas.1205271109 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2012 Oct 16;109(42):17087-92. doi: 
      10.1073/pnas.1205271109. Epub 2012 Oct 1.