PMID- 10648867
OWN - NLM
STAT- MEDLINE
DCOM- 20000308
LR  - 20211203
IS  - 0165-3806 (Print)
IS  - 0165-3806 (Linking)
VI  - 119
IP  - 1
DP  - 2000 Jan 3
TI  - MEK inhibitors block BDNF-dependent and -independent expression of GABA(A) 
      receptor subunit mRNAs in cultured mouse cerebellar granule neurons.
PG  - 1-10
AB  - Brain-derived neurotrophic factor (BDNF) can regulate the maturation of 
      developing cerebellar granule neurons. Within 1-2 days of culture, BDNF induces 
      the expression of granule neuron terminal differentiation markers, particularly 
      GABA(A) receptor alpha6 subunit (GABA(A)alpha6) mRNA. Other trophic factors 
      including insulin-like growth factor, the neurotrophin NT-3, pituitary adenylate 
      cyclase-activating polypeptide (PACAP), and fetal bovine serum failed to induce 
      this early expression. The expression of other GABA(A) receptor subunits, 
      including alpha1 and gamma2, was also enhanced by exposure of developing granule 
      neurons to BDNF. This BDNF-dependent expression of GABA(A) receptor subunit mRNAs 
      could be effectively blocked by treatment with the mitogen-activated protein 
      kinase kinase (MEK) inhibitors, PD98059 or U0126. In the absence of BDNF, 
      GABA(A)alpha6 expression occurs but not until 3-4 days of culture. This 
      BDNF-independent expression of GABA(A)alpha6 was also inhibited by PD98059. 
      Further studies showed that the BDNF-dependent expression GABA(A)alpha6 could 
      also be reduced by LY294002, an inhibitor of the phosphatidylinositol 3-kinase, 
      or depolarizing concentrations of KCl. These results thus suggest that both 
      BDNF-dependent and -independent expressions of GABA(A) receptor subunits require 
      the activation of MEK and the mitogen-activated protein kinase (MAPK) pathway. 
      However, it is also likely that other signaling pathways modulate this maturation 
      process.
FAU - Bulleit, R F
AU  - Bulleit RF
AD  - Department of Pharmacology, University of Maryland School of Medicine, Baltimore, 
      MD 21201, USA. bbulleit@promega.com
FAU - Hsieh, T
AU  - Hsieh T
LA  - eng
GR  - ES/OD08087/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res Dev Brain Res
JT  - Brain research. Developmental brain research
JID - 8908639
RN  - 0 (Adcyap1 protein, mouse)
RN  - 0 (Blood Proteins)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Chromones)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Morpholines)
RN  - 0 (Neuropeptides)
RN  - 0 (Neurotrophin 3)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Pituitary Adenylate Cyclase-Activating Polypeptide)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, GABA-A)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - 71-62-5 (Veratridine)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 1)
RN  - EC 2.7.12.2 (Map2k1 protein, mouse)
RN  - EC 2.7.12.2 (Mitogen-Activated Protein Kinase Kinases)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Animals
MH  - Blood Proteins/pharmacology
MH  - Brain-Derived Neurotrophic Factor/*metabolism/pharmacology
MH  - Calcium Channel Blockers/pharmacology
MH  - Cell Differentiation/physiology
MH  - Cells, Cultured
MH  - Cerebellum/cytology/*physiology
MH  - Chromones/pharmacology
MH  - Cytomegalovirus/genetics
MH  - Cytoplasmic Granules
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - Gene Expression Regulation/physiology
MH  - Genes, Reporter
MH  - Insulin-Like Growth Factor I/pharmacology
MH  - MAP Kinase Kinase 1
MH  - MAP Kinase Signaling System/drug effects/*physiology
MH  - Mice
MH  - Mitogen-Activated Protein Kinase Kinases/*antagonists & inhibitors
MH  - Morpholines/pharmacology
MH  - Neurons/cytology/*enzymology
MH  - Neuropeptides/pharmacology
MH  - Neurotrophin 3/pharmacology
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Pituitary Adenylate Cyclase-Activating Polypeptide
MH  - Promoter Regions, Genetic/genetics
MH  - Protein Serine-Threonine Kinases/*antagonists & inhibitors
MH  - RNA, Messenger/*biosynthesis
MH  - Receptors, GABA-A/*genetics
MH  - Veratridine/pharmacology
EDAT- 2000/01/29 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/01/29 09:00
PHST- 2000/01/29 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/01/29 09:00 [entrez]
AID - S0165380699001194 [pii]
AID - 10.1016/s0165-3806(99)00119-4 [doi]
PST - ppublish
SO  - Brain Res Dev Brain Res. 2000 Jan 3;119(1):1-10. doi: 
      10.1016/s0165-3806(99)00119-4.