PMID- 11739615
OWN - NLM
STAT- MEDLINE
DCOM- 20020117
LR  - 20191210
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 79
IP  - 5
DP  - 2001 Dec
TI  - Role of phosphatidylinositide 3-kinase in brain-derived neurotrophic 
      factor-induced DARPP-32 expression in medium size spiny neurons in vitro.
PG  - 1027-32
AB  - Brain-derived neurotrophic factor (BDNF) regulates several properties of striatal 
      dopaminoceptive medium-sized spiny neurons (MSNs) in vivo and in vitro, including 
      expression levels of DARPP-32 (dopamine and cyclic adenosine 
      3',5'-monophosphate-regulated phosphoprotein, 32 kDa). DARPP-32 is expressed in 
      96% of the MSNs, and is a key modulator of dopamine actions. We investigated the 
      intracellular signal transduction pathways activated by BDNF in MSNs and via 
      which BDNF induces DARPP-32 expression. We found that phosphorylation of the 
      cyclic AMP response element binding protein (CREB) is only transiently increased 
      following stimulation of MSNs by BDNF, whereas increased phosphorylation of the 
      extracellular signal regulated kinases 1 and 2 (Erk1/2) and Akt is sustained for 
      longer than 4 h. Treatment of cultures with inhibitors of mitogen-activated 
      protein kinase kinase (MEK) or phosphatidylinositide 3-kinase (PI3K) showed that 
      the majority of the BDNF-induced increase in DARPP-32 requires the PI3K pathway. 
      We also found that inhibition of PI3K reduces BDNF-induced Erk phosphorylation, 
      indicating that cross-talk between these pathways may play a prominent role in 
      MSNs.
FAU - Stroppolo, A
AU  - Stroppolo A
AD  - The Nathan Kline Institute, Orangeburg, New York 10962, USA.
FAU - Guinea, B
AU  - Guinea B
FAU - Tian, C
AU  - Tian C
FAU - Sommer, J
AU  - Sommer J
FAU - Ehrlich, M E
AU  - Ehrlich ME
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Chromones)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Dopamine and cAMP-Regulated Phosphoprotein 32)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Morpholines)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Phosphoproteins)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Blotting, Western
MH  - Brain Chemistry/*drug effects
MH  - Brain-Derived Neurotrophic Factor/antagonists & inhibitors/*pharmacology
MH  - Cell Size
MH  - Chromones/pharmacology
MH  - Cyclic AMP Response Element-Binding Protein/metabolism
MH  - Dopamine and cAMP-Regulated Phosphoprotein 32
MH  - Enzyme Inhibitors/pharmacology
MH  - Female
MH  - Mice
MH  - Mitogen-Activated Protein Kinase 1/metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Morpholines/pharmacology
MH  - *Nerve Tissue Proteins
MH  - Neurons/drug effects/*metabolism/ultrastructure
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Phosphoproteins/*biosynthesis
MH  - Phosphorylation
MH  - Pregnancy
MH  - Signal Transduction/drug effects
EDAT- 2001/12/12 10:00
MHDA- 2002/01/18 10:01
CRDT- 2001/12/12 10:00
PHST- 2001/12/12 10:00 [pubmed]
PHST- 2002/01/18 10:01 [medline]
PHST- 2001/12/12 10:00 [entrez]
AID - 10.1046/j.1471-4159.2001.00651.x [doi]
PST - ppublish
SO  - J Neurochem. 2001 Dec;79(5):1027-32. doi: 10.1046/j.1471-4159.2001.00651.x.