PMID- 17913925
OWN - NLM
STAT- MEDLINE
DCOM- 20071126
LR  - 20211020
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 27
IP  - 40
DP  - 2007 Oct 3
TI  - Brain-derived neurotrophic factor expression and respiratory function improve 
      after ampakine treatment in a mouse model of Rett syndrome.
PG  - 10912-7
AB  - Rett syndrome (RTT) is caused by loss-of-function mutations in the gene encoding 
      methyl-CpG-binding protein 2 (MeCP2). Although MeCP2 is thought to act as a 
      transcriptional repressor of brain-derived neurotrophic factor (BDNF), Mecp2 null 
      mice, which develop an RTT-like phenotype, exhibit progressive deficits in BDNF 
      expression. These deficits are particularly significant in the brainstem and 
      nodose cranial sensory ganglia (NGs), structures critical for cardiorespiratory 
      homeostasis, and may be linked to the severe respiratory abnormalities 
      characteristic of RTT. Therefore, the present study used Mecp2 null mice to 
      further define the role of MeCP2 in regulation of BDNF expression and neural 
      function, focusing on NG neurons and respiratory control. We find that mutant 
      neurons express significantly lower levels of BDNF than wild-type cells in vitro, 
      as in vivo, under both depolarizing and nondepolarizing conditions. However, BDNF 
      levels in mutant NG cells can be increased by chronic depolarization in vitro or 
      by treatment of Mecp2 null mice with CX546, an ampakine drug that facilitates 
      activation of glutamatergic AMPA receptors. Ampakine-treated Mecp2 null mice also 
      exhibit marked functional improvement, characterized by restoration of normal 
      breathing frequency and minute volume. These data demonstrate that BDNF 
      expression remains plastic in Mecp2 null mice and raise the possibility that 
      ampakine compounds could be of therapeutic value in the treatment of RTT.
FAU - Ogier, Michael
AU  - Ogier M
AD  - Department of Neurosciences, Case Western Reserve University School of Medicine, 
      Cleveland, Ohio 44106, USA.
FAU - Wang, Hong
AU  - Wang H
FAU - Hong, Elizabeth
AU  - Hong E
FAU - Wang, Qifang
AU  - Wang Q
FAU - Greenberg, Michael E
AU  - Greenberg ME
FAU - Katz, David M
AU  - Katz DM
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (1-(1,4-benzodioxan-6-ylcarbonyl)piperidine)
RN  - 0 (Anesthetics, Local)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Depsipeptides)
RN  - 0 (Dioxoles)
RN  - 0 (Mecp2 protein, mouse)
RN  - 0 (Methyl-CpG-Binding Protein 2)
RN  - 0 (Piperidines)
RN  - 0 (RNA, Messenger)
RN  - 0 (respirantin)
RN  - 4368-28-9 (Tetrodotoxin)
SB  - IM
MH  - Analysis of Variance
MH  - Anesthetics, Local/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Cells, Cultured
MH  - Depsipeptides/*drug effects
MH  - Dioxoles/*therapeutic use
MH  - Disease Models, Animal
MH  - Gene Expression Regulation/*drug effects/genetics
MH  - Methyl-CpG-Binding Protein 2/genetics
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neurons/drug effects/metabolism
MH  - Nodose Ganglion/cytology
MH  - Piperidines/*therapeutic use
MH  - Plethysmography/methods
MH  - RNA, Messenger/biosynthesis
MH  - Rett Syndrome/*drug therapy/*physiopathology
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Tetrodotoxin/pharmacology
PMC - PMC6672830
EDAT- 2007/10/05 09:00
MHDA- 2007/12/06 09:00
PMCR- 2008/04/03
CRDT- 2007/10/05 09:00
PHST- 2007/10/05 09:00 [pubmed]
PHST- 2007/12/06 09:00 [medline]
PHST- 2007/10/05 09:00 [entrez]
PHST- 2008/04/03 00:00 [pmc-release]
AID - 27/40/10912 [pii]
AID - 3271023 [pii]
AID - 10.1523/JNEUROSCI.1869-07.2007 [doi]
PST - ppublish
SO  - J Neurosci. 2007 Oct 3;27(40):10912-7. doi: 10.1523/JNEUROSCI.1869-07.2007.