PMID- 16876982
OWN - NLM
STAT- MEDLINE
DCOM- 20070410
LR  - 20191210
IS  - 0898-6568 (Print)
IS  - 0898-6568 (Linking)
VI  - 19
IP  - 1
DP  - 2007 Jan
TI  - Norepinephrine induces BDNF and activates the PI-3K and MAPK cascades in 
      embryonic hippocampal neurons.
PG  - 114-28
AB  - Both antidepressant treatment and physical exercise have been shown to increase 
      circulating levels of norepinephine (NE) and hippocampal brain-derived 
      neurotrophic factor (BDNF). Increases in BDNF have been shown to be associated 
      with enhanced dendritic arborization and neuronal survival, which forms the 
      theoretical basis of the Neurotrophin Hypothesis of antidepressant action. Using 
      isolated embryonic hippocampal neurons and immunoblotting, we show that 
      application of NE increases BDNF and phosphorylated Trk, and that these increases 
      can be prevented by ERK and PI-3K inhibitors. In addition, NE-induced increases 
      in phospho-ERK2 and PI-3K were each suppressed by a PI-3K and MAPK inhibitor, 
      respectively. Furthermore, phosphorylation of cAMP-response element binding 
      (CREB) protein was also increased by NE and brought down to baseline levels by 
      MAPK and PI-3K inhibitors. And finally, because both the MAPK and PI-3K 
      inhibitors suppress phosphorylation of both TrkB (upstream) and CREB 
      (downstream), these results indicate that NE-induced BDNF expression follows a 
      cyclic pathway, reminiscent of a positive feedback loop. The results of this 
      study provide an in vitro model of the intracellular signaling mechanisms 
      activated by NE, via ligand-G-protein-coupled receptor (GPCR)-to-BDNF-RTK 
      transactivation, that is putatively thought to occur in vivo as a result of 
      excitatory neural activity.
FAU - Chen, M J
AU  - Chen MJ
AD  - California State University, Los Angeles, Department of Biological Sciences, 5151 
      State University Dr., Los Angeles, CA 90032, USA. mchen@calstatela.edu
FAU - Nguyen, T V
AU  - Nguyen TV
FAU - Pike, C J
AU  - Pike CJ
FAU - Russo-Neustadt, A A
AU  - Russo-Neustadt AA
LA  - eng
GR  - MH 59776/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20060607
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Protein Kinase Inhibitors)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Cells, Cultured
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Embryo, Mammalian/cytology
MH  - Enzyme Activation
MH  - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/*metabolism
MH  - Female
MH  - Hippocampus/cytology
MH  - Neurons/drug effects/*metabolism
MH  - Norepinephrine/*pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphorylation
MH  - Pregnancy
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Rats
MH  - Receptor, trkB/metabolism
MH  - Signal Transduction
EDAT- 2006/08/01 09:00
MHDA- 2007/04/11 09:00
CRDT- 2006/08/01 09:00
PHST- 2006/05/11 00:00 [received]
PHST- 2006/05/29 00:00 [accepted]
PHST- 2006/08/01 09:00 [pubmed]
PHST- 2007/04/11 09:00 [medline]
PHST- 2006/08/01 09:00 [entrez]
AID - S0898-6568(06)00142-2 [pii]
AID - 10.1016/j.cellsig.2006.05.028 [doi]
PST - ppublish
SO  - Cell Signal. 2007 Jan;19(1):114-28. doi: 10.1016/j.cellsig.2006.05.028. Epub 2006 
      Jun 7.