Phosphatidylinositol 3-kinase activation is required for stress protocol-induced modification of hippocampal synaptic plasticity

Ping Chun Yang, Chih Hao Yang, Chiung Chun Huang, Kuei Sen Hsu

研究成果: 雜誌貢獻文章

60 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)2631-2643
頁數13
期刊Journal of Biological Chemistry
283
發行號5
DOIs
出版狀態已發佈 - 二月 1 2008
對外發佈Yes

指紋

Phosphatidylinositol 3-Kinase
Neuronal Plasticity
Plasticity
Chemical activation
Long-Term Potentiation
Sirolimus
3-Phosphoinositide-Dependent Protein Kinases
70-kDa Ribosomal Protein S6 Kinases
Eukaryotic Initiation Factors
2-Amino-5-phosphonovalerate
Proto-Oncogene Proteins c-akt
Phosphorylation
2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
Antisense Oligonucleotides
Brain-Derived Neurotrophic Factor
Glucocorticoid Receptors
N-Methyl-D-Aspartate Receptors
Immunoblotting
Shock
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

引用此文

Phosphatidylinositol 3-kinase activation is required for stress protocol-induced modification of hippocampal synaptic plasticity. / Yang, Ping Chun; Yang, Chih Hao; Huang, Chiung Chun; Hsu, Kuei Sen.

於: Journal of Biological Chemistry, 卷 283, 編號 5, 01.02.2008, p. 2631-2643.

研究成果: 雜誌貢獻文章

@article{e555ab81b72347bd9b3dfb12f9adf7e3,
title = "Phosphatidylinositol 3-kinase activation is required for stress protocol-induced modification of hippocampal synaptic plasticity",
abstract = "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.",
author = "Yang, {Ping Chun} and Yang, {Chih Hao} and Huang, {Chiung Chun} and Hsu, {Kuei Sen}",
year = "2008",
month = "2",
day = "1",
doi = "10.1074/jbc.M706954200",
language = "English",
volume = "283",
pages = "2631--2643",
journal = "Journal of Biological Chemistry",
issn = "0021-9258",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "5",

}

TY - JOUR

T1 - Phosphatidylinositol 3-kinase activation is required for stress protocol-induced modification of hippocampal synaptic plasticity

AU - Yang, Ping Chun

AU - Yang, Chih Hao

AU - Huang, Chiung Chun

AU - Hsu, Kuei Sen

PY - 2008/2/1

Y1 - 2008/2/1

N2 - 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.

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.

UR - http://www.scopus.com/inward/record.url?scp=41449088031&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=41449088031&partnerID=8YFLogxK

U2 - 10.1074/jbc.M706954200

DO - 10.1074/jbc.M706954200

M3 - Article

C2 - 18057005

AN - SCOPUS:41449088031

VL - 283

SP - 2631

EP - 2643

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 5

ER -