PMID- 18057005
OWN - NLM
STAT- MEDLINE
DCOM- 20080402
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 283
IP  - 5
DP  - 2008 Feb 1
TI  - Phosphatidylinositol 3-kinase activation is required for stress protocol-induced 
      modification of hippocampal synaptic plasticity.
PG  - 2631-43
AB  - Stress dramatically affects the induction of hippocampal synaptic plasticity; 
      however, the molecular details of how it does so remain unclear. 
      Phosphatidylinositol 3-kinase (PI3K) signaling plays a crucial role in promoting 
      neuronal survival and neuroplasticity, but its role, if any, in stress-induced 
      alterations of long term potentiation (LTP) and long term depression (LTD) is 
      unknown. We found here that inhibitors of PI3K signaling blocked the effects of 
      acute restraint-tail shock stress protocol on LTP and LTD. Therefore, the purpose 
      of the present study is to explore the signaling events involving PI3K in terms 
      of its role in mediating stress protocol-induced alterations of LTP and LTD. We 
      found that stress protocol-induced PI3K activation can be blocked by various 
      inhibitors, including RU38486 for glucocorticoid receptors, LY294002 for PI3K, 
      and dl-2-amino-5-phosphonopentanoic acid for N-methyl-D-aspartate receptors or 
      brain-derived neurotrophic factor antisense oligonucleotides. Also, 
      immunoblotting analyses revealed that stress protocol induced a profound and 
      prolonged phosphorylation of numbers of PI3K downstream effectors, including 
      3-phosphoinositide-dependent protein kinase-1, protein kinase B, mammalian target 
      of rapamycin (mTOR), p70 S6 kinase, and eukaryotic initiation factor 4B in 
      hippocampal CA1 homogenate, which was prevented by the PI3K inhibitor 
      pretreatment. More importantly, we found that stress protocol significantly 
      increased the protein expression of dendritic scaffolding protein PSD-95 
      (postsynaptic density-95), which is known to be involved in LTP and LTD, in an 
      mTOR-dependent manner. These results identify a key role of PI3K signaling in 
      mediating the stress protocol-induced modification of hippocampal synaptic 
      plasticity and further suggest that PI3K may do so by invoking the protein 
      expression of PSD-95.
FAU - Yang, Ping-Chun
AU  - Yang PC
AD  - Department of Pharmacology, College of Medicine, National Cheng-Kung University, 
      1 University Road, Tainan, Taiwan.
FAU - Yang, Chih-Hao
AU  - Yang CH
FAU - Huang, Chiung-Chun
AU  - Huang CC
FAU - Hsu, Kuei-Sen
AU  - Hsu KS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20071205
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Chromones)
RN  - 0 (Disks Large Homolog 4 Protein)
RN  - 0 (Dlg4 protein, rat)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Morpholines)
RN  - 0 (Oligodeoxyribonucleotides, Antisense)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 320T6RNW1F (Mifepristone)
RN  - 76726-92-6 (2-Amino-5-phosphonovalerate)
SB  - IM
MH  - 2-Amino-5-phosphonovalerate/pharmacology
MH  - Animals
MH  - Base Sequence
MH  - Brain-Derived Neurotrophic Factor/antagonists & inhibitors
MH  - Chromones/pharmacology
MH  - Disks Large Homolog 4 Protein
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Hippocampus/drug effects/*physiology
MH  - Intracellular Signaling Peptides and Proteins/metabolism
MH  - Long-Term Potentiation
MH  - Long-Term Synaptic Depression
MH  - Male
MH  - Membrane Proteins/metabolism
MH  - Mifepristone/pharmacology
MH  - Models, Neurological
MH  - Morpholines/pharmacology
MH  - Neuronal Plasticity/*physiology
MH  - Oligodeoxyribonucleotides, Antisense/pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Glucocorticoid/antagonists & inhibitors
MH  - Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
MH  - Signal Transduction
MH  - Stress, Physiological/physiopathology
EDAT- 2007/12/07 09:00
MHDA- 2008/04/03 09:00
CRDT- 2007/12/07 09:00
PHST- 2007/12/07 09:00 [pubmed]
PHST- 2008/04/03 09:00 [medline]
PHST- 2007/12/07 09:00 [entrez]
AID - S0021-9258(20)55512-9 [pii]
AID - 10.1074/jbc.M706954200 [doi]
PST - ppublish
SO  - J Biol Chem. 2008 Feb 1;283(5):2631-43. doi: 10.1074/jbc.M706954200. Epub 2007 
      Dec 5.