碩士 / 國立成功大學 / 藥理學研究所 / 95 / Stress has been shown to dramatically affect the induction of hippocampal synaptic plasticity; however, the molecular details of how it does so remain unclear. Although 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 LTP or LTD is unknown. We firstly found here that inhibitors of PI3K signaling blocked the effect of stress on LTP and LTD. Therefore, the purpose of the present study is to elucidate the signaling events involving PI3K in terms of its role in mediating stress-induced alterations of LTP and LTD. We found that stress-induced PI3K activation can be blocked by various inhibitors including RU38486 for glucocorticoid receptors, LY294002 for PI3K, DL-2-amino-5-phosphonopentanoic acid for NMDA receptors, K252a for tyrosine kinase receptors, or BDNF antisense oligonucleotides. Also, immunoblotting analyses revealed that stress induced a profound and prolonged phosphorylation of a number of PI3K downstream effectors, including 3-phosphoinositide-dependent protein kinase-1 (PDK1), protein kinase B, mammalian target of rapamycin (mTOR), p70S6 kinase and eukaryotic initiation factor 4B (eIF4B) in hippocampal CA1 homogenates, which were prevented by the PI3K inhibitor pretreatment. More importantly, we found that stress significantly increased the protein expression of dendritic scaffolding protein postsynaptic density-95, which is known to involve in LTP and LTD, in an mTOR-dependent manner. These results identify a key role of PI3K signaling in mediating the stress-induced modification of hippocampal synaptic plasticity and further suggest that PI3K may do so by invoking the protein expression of PSD95.
| Identifer | oai:union.ndltd.org:TW/095NCKU5550011 |
| Date | January 2007 |
| Creators | Ping-chun Yang, 楊秉鈞 |
| Contributors | Kuei-sen Hsu, 許桂森 |
| Source Sets | National Digital Library of Theses and Dissertations in Taiwan |
| Language | zh-TW |
| Detected Language | English |
| Type | 學位論文 ; thesis |
| Format | 125 |
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