PMID- 16901909
OWN - NLM
STAT- MEDLINE
DCOM- 20061130
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 281
IP  - 40
DP  - 2006 Oct 6
TI  - Brain-derived neurotrophic factor (BDNF)-induced synthesis of early growth 
      response factor 3 (Egr3) controls the levels of type A GABA receptor alpha 4 
      subunits in hippocampal neurons.
PG  - 29431-5
AB  - Altered function of gamma-aminobutyric acid type A receptors (GABA(A)Rs) in 
      dentate granule cells of the hippocampus has been associated with temporal lobe 
      epilepsy (TLE) in humans and in animal models of TLE. Such altered receptor 
      function (including increased inhibition by zinc and lack of modulation by 
      benzodiazepines) is related, in part, to changes in the mRNA levels of certain 
      GABA(A)R subunits, including alpha4, and may play a role in epileptogenesis. The 
      majority of GABA(A)Rs that contain alpha4 subunits are extra-synaptic due to lack 
      of the gamma2 subunit and presence of delta. However, it has been hypothesized 
      that seizure activity may result in expression of synaptic receptors with altered 
      properties driven by an increased pool of alpha4 subunits. Results of our 
      previous work suggests that signaling via protein kinase C (PKC) and early growth 
      response factor 3 (Egr3) is the plasticity trigger for aberrant alpha4 subunit 
      gene (GABRA4) expression after status epilepticus. We now report that brain 
      derived neurotrophic factor (BDNF) is the endogenous signal that induces Egr3 
      expression via a PKC/MAPK-dependent pathway. Taken together with the fact that 
      blockade of tyrosine kinase (Trk) neurotrophin receptors reduces basal GABRA4 
      promoter activity by 50%, our findings support a role for BDNF as the mediator of 
      Egr3-induced GABRA4 regulation in developing neurons and epilepsy and, moreover, 
      suggest that BDNF may alter inhibitory processing in the brain by regulating the 
      balance between phasic and tonic inhibition.
FAU - Roberts, Daniel S
AU  - Roberts DS
AD  - Laboratory of Molecular Neurobiology, Department of Pharmacology, Boston 
      University School of Medicine, Boston, Massachusetts 02118, USA.
FAU - Hu, Yinghui
AU  - Hu Y
FAU - Lund, Ingrid V
AU  - Lund IV
FAU - Brooks-Kayal, Amy R
AU  - Brooks-Kayal AR
FAU - Russek, Shelley J
AU  - Russek SJ
LA  - eng
GR  - NS050393/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060810
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (EGR3 protein, human)
RN  - 0 (GABRA4 protein, human)
RN  - 0 (Protein Subunits)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, GABA-A)
RN  - 144516-98-3 (Early Growth Response Protein 3)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Cells, Cultured
MH  - Early Growth Response Protein 3/*biosynthesis/genetics
MH  - Hippocampus/cytology/*metabolism
MH  - Neurons/*metabolism
MH  - Protein Subunits/*metabolism
MH  - RNA, Messenger/biosynthesis
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, GABA-A/*metabolism
EDAT- 2006/08/12 09:00
MHDA- 2006/12/09 09:00
CRDT- 2006/08/12 09:00
PHST- 2006/08/12 09:00 [pubmed]
PHST- 2006/12/09 09:00 [medline]
PHST- 2006/08/12 09:00 [entrez]
AID - S0021-9258(19)33848-7 [pii]
AID - 10.1074/jbc.C600167200 [doi]
PST - ppublish
SO  - J Biol Chem. 2006 Oct 6;281(40):29431-5. doi: 10.1074/jbc.C600167200. Epub 2006 
      Aug 10.