PMID- 10501191
OWN - NLM
STAT- MEDLINE
DCOM- 19991014
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 73
IP  - 4
DP  - 1999 Oct
TI  - Brain-derived neurotrophic factor exerts opposing effects on beta2-adrenergic 
      receptor according to depolarization status of cerebellar neurons.
PG  - 1467-76
AB  - To investigate the molecular mechanisms underlying brain-derived neurotrophic 
      factor (BDNF)-controlled synaptic plasticity, we studied beta2-adrenergic 
      receptor (beta2-AR) expression in cultured cerebellar granule cells. We show 
      that, depending on the state of depolarization, BDNF exerts opposite effects on 
      beta2-AR expression. In neurons maintained in low K+ medium (5 mM K+) that will 
      enter apoptosis, BDNF increases beta2-AR and beta2-AR transcripts. In contrast, 
      in depolarized neurons (high K+ medium, 25 mM K+) BDNF represses beta2-AR 
      expression. The use of reporter genes (driven by the beta2-AR promoter or 
      restricted regulatory elements) revealed that BDNF exerts its opposite effects at 
      the transcriptional level by recruiting a cyclic AMP response element (CRE) and 
      the trans-acting factor CRE binding protein. These results provide the first 
      evidence that a neurotrophin, e.g., BDNF, may exert an opposite effect on 
      receptor expression and function (beta2-AR) according to the depolarization 
      status of the neuron. Based on this finding, we propose that BDNF not only 
      mediates neuronal survival, but is also involved in the modulation of the general 
      sensitivity of the neuron to external signals, thus maintaining its optimal 
      functional integration within the neuronal network.
FAU - Gaiddon, C
AU  - Gaiddon C
AD  - UMR 7519 CNRS, Institut de Physiologie et de Chimie Biologique, Universite Louis 
      Pasteur, Strasbourg, France.
FAU - Larmet, Y
AU  - Larmet Y
FAU - Trinh, E
AU  - Trinh E
FAU - Boutillier, A L
AU  - Boutillier AL
FAU - Sommer, B
AU  - Sommer B
FAU - Loeffler, J P
AU  - Loeffler JP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 0 (Recombinant Fusion Proteins)
RN  - E0399OZS9N (Cyclic AMP)
RN  - L628TT009W (Isoproterenol)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Base Sequence
MH  - Brain-Derived Neurotrophic Factor/*pharmacology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cerebellum/cytology/*physiology
MH  - Cyclic AMP/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Humans
MH  - Isoproterenol/pharmacology
MH  - Kinetics
MH  - Mutagenesis, Site-Directed
MH  - Neurons/cytology/drug effects/*physiology
MH  - Potassium/pharmacology
MH  - Promoter Regions, Genetic
MH  - Rats
MH  - Receptors, Adrenergic, beta-2/genetics/*physiology
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transcription, Genetic/*drug effects
MH  - Transfection
EDAT- 1999/09/29 00:00
MHDA- 1999/09/29 00:01
CRDT- 1999/09/29 00:00
PHST- 1999/09/29 00:00 [pubmed]
PHST- 1999/09/29 00:01 [medline]
PHST- 1999/09/29 00:00 [entrez]
AID - 10.1046/j.1471-4159.1999.0731467.x [doi]
PST - ppublish
SO  - J Neurochem. 1999 Oct;73(4):1467-76. doi: 10.1046/j.1471-4159.1999.0731467.x.