PMID- 11689163
OWN - NLM
STAT- MEDLINE
DCOM- 20020103
LR  - 20190614
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 919
IP  - 1
DP  - 2001 Nov 16
TI  - Induction of functional and morphological expression of neuropeptide Y (NPY) in 
      cortical cultures by brain-derived neurotrophic factor (BDNF): evidence for a 
      requirement for extracellular-regulated kinase (ERK)-dependent and 
      ERK-independent mechanisms.
PG  - 57-69
AB  - Previous studies have demonstrated that brain-derived neurotrophic factor (BDNF) 
      induces expression of neuropeptide Y (NPY) neurons in aggregate cultures derived 
      from the fetal rat cortex. Using BDNF induction of NPY production and neurite 
      extension of NPY neurons as functional and morphological criteria, respectively, 
      we addressed the question: Does BDNF activate the extracellular-regulated kinase 
      (ERK) pathway and if so, is activated (phosphorylated, P)-ERK required for the 
      induction of both the functional and morphological expression of NPY? BDNF led to 
      a rapid (30 min) and sustained (6 h) phosphorylation of ERK. PD98059 (PD, a 
      specific inhibitor of the ERK kinase MEK), drastically inhibited, LY294002 (LY, a 
      specific inhibitor of phosphatidylinositol-3-kinase, PI-3K) partially inhibited, 
      and GF 109203X (GF, a specific inhibitor of protein kinase C) did not inhibit 
      phosphorylation of ERK. A 24-h exposure to BDNF led to approximately 2-fold 
      increase in the total culture content of NPY ( approximately 60% of which was 
      secreted and approximately 40% remained in the aggregates) and to an abundance of 
      neurite-bearing NPY neurons. BDNF-induced NPY produced and secreted into the 
      medium was inhibited 73% by PD, 52% by LY and not at all by GF. In contrast, 
      BDNF-induced NPY produced and sequestered in the aggregates was not inhibited by 
      any of these inhibitors, suggesting a role for the ERK pathway in induced 
      secretion of NPY. PD or LY did not inhibit BDNF-induced abundance of 
      neurite-bearing NPY neurons. K252a (an inhibitor of TrkB-tyrosine kinase) 
      abolished all the effects of BDNF assessed in our cultures. In summary, we 
      demonstrate that TrkB-mediated activation of the ERK pathway is preferentially 
      required for BDNF induction of NPY produced and secreted but not for the 
      induction of the expression of neurite-bearing NPY neurons. Thus, BDNF induction 
      of the functional and morphological expression of NPY is brought about by 
      ERK-dependent and ERK-independent mechanisms.
FAU - Barnea, A
AU  - Barnea A
AD  - Department of Obstetrics and Gynecology, The University of Texas Southwestern 
      Medical Center at Dallas, 5323 Harry Hines Blvd., Dallas, TX 75390-9032, USA. 
      ayalla.barnea@utsouthwestern.edu
FAU - Roberts, J
AU  - Roberts J
LA  - eng
GR  - MH4184/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Neuropeptide Y)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*physiology
MH  - Cell Aggregation
MH  - Cells, Cultured
MH  - Cerebral Cortex/*cytology/enzymology/*metabolism
MH  - Enzyme Activation
MH  - Female
MH  - Fetus
MH  - Immunohistochemistry
MH  - MAP Kinase Signaling System
MH  - Mitogen-Activated Protein Kinases/metabolism/*physiology
MH  - Neurons/cytology/enzymology/metabolism
MH  - Neuropeptide Y/*biosynthesis
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/metabolism/physiology
EDAT- 2001/11/02 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/11/02 10:00
PHST- 2001/11/02 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/11/02 10:00 [entrez]
AID - S0006-8993(01)02999-7 [pii]
AID - 10.1016/s0006-8993(01)02999-7 [doi]
PST - ppublish
SO  - Brain Res. 2001 Nov 16;919(1):57-69. doi: 10.1016/s0006-8993(01)02999-7.