PMID- 17050729
OWN - NLM
STAT- MEDLINE
DCOM- 20061114
LR  - 20200225
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Print)
IS  - 0270-6474 (Linking)
VI  - 26
IP  - 42
DP  - 2006 Oct 18
TI  - Dysregulation of brain-derived neurotrophic factor expression and neurosecretory 
      function in Mecp2 null mice.
PG  - 10911-5
AB  - Disruptions in brain-derived neurotrophic factor (BDNF) expression are proposed 
      to contribute to the molecular pathogenesis of Rett syndrome (RTT), a severe 
      neurological disorder caused by loss-of-function mutations in methyl-CpG-binding 
      protein-2 (MeCP2). Although MeCP2 is a transcriptional regulator of BDNF, it is 
      unknown how MeCP2 mutations affect transsynaptic BDNF signaling. Our findings 
      demonstrate an early, abnormal neurosecretory phenotype in MeCP2-deficient 
      neurons characterized by significant increases in the percentage of cellular BDNF 
      content available for release. However, loss of MeCP2 also results in deficits in 
      total cell BDNF content that are developmentally regulated in a 
      cell-type-specific manner. Thus, the net effect of MeCP2 loss on absolute BDNF 
      secretion changes with age and is determined by both the amount of BDNF available 
      for release and progressive declines in total cellular BDNF. We propose, 
      therefore, that loss of MeCP2 function disrupts transsynaptic BDNF signaling by 
      perturbing the normal balance between BDNF protein levels and secretion. However, 
      mutant neurons are capable of secreting wild-type levels of BDNF in response to 
      high-frequency electrical stimulation. In addition, we found elevated exocytic 
      function in Mecp2(-/y) adrenal chromaffin cells, indicating that the Mecp2 null 
      mutation is associated with alterations of neurosecretion that are not restricted 
      to BDNF. These findings are the first examples of abnormal neuropeptide and 
      catecholamine secretion in a mouse model of RTT.
FAU - Wang, Hong
AU  - Wang H
AD  - Department of Neurosciences, Case Western Reserve University School of Medicine, 
      Cleveland, Ohio 44106-4975, USA.
FAU - Chan, Shyue-an
AU  - Chan SA
FAU - Ogier, Michael
AU  - Ogier M
FAU - Hellard, David
AU  - Hellard D
FAU - Wang, Qifang
AU  - Wang Q
FAU - Smith, Corey
AU  - Smith C
FAU - Katz, David M
AU  - Katz DM
LA  - eng
PT  - Comparative Study
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 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Methyl-CpG-Binding Protein 2)
SB  - IM
MH  - Adrenal Glands/metabolism
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis/*genetics/physiology
MH  - Cells, Cultured
MH  - Gene Expression Regulation/*genetics
MH  - Methyl-CpG-Binding Protein 2/deficiency/*genetics/*metabolism
MH  - Mice
MH  - Mice, Knockout
MH  - Signal Transduction/genetics
MH  - Synapses/genetics/*metabolism
PMC - PMC6674736
EDAT- 2006/10/20 09:00
MHDA- 2006/11/15 09:00
PMCR- 2007/04/18
CRDT- 2006/10/20 09:00
PHST- 2006/10/20 09:00 [pubmed]
PHST- 2006/11/15 09:00 [medline]
PHST- 2006/10/20 09:00 [entrez]
PHST- 2007/04/18 00:00 [pmc-release]
AID - 26/42/10911 [pii]
AID - 3154773 [pii]
AID - 10.1523/JNEUROSCI.1810-06.2006 [doi]
PST - ppublish
SO  - J Neurosci. 2006 Oct 18;26(42):10911-5. doi: 10.1523/JNEUROSCI.1810-06.2006.