碩士 / 國立成功大學 / 藥理學研究所 / 98 / Structural and synaptic plasticity are generally thought to be the cellular mechanisms underlying the refinement of neuronal connections in the developing nervous systems and contributing to the processes of learning and memory in the mature brain. Epidermal growth factor receptor substrate 8 (Eps8) was originally considered as an intracellular substrates for the kinase activity of the EGF receptor implicated in the regulation of actin cytoskeleton. Recent study has reported that mice lacking Eps8 are resistant to some acute intoxicating effects of ethanol and showed increased ethanol consumption. In the cerebellum, Eps8 was found to be densely expressed on unipolar brush cells and moderately expressed on granule cells. So far, the expression of Eps8 in the hippocampus and its role in hippocampal functions remain unknown. In this study, we found that the peak expression of Eps8 in rat hippocampus was between postnatal day 7 to 28, a period that is known to be important for the synaptogenesis in vivo. In addition, the Eps8 protein was enriched in synaptosomes and postsynaptic fractions (synaptoneurosomes) from postnatal day 14 hippocampus. Overexpressed Eps8 markedly increased the dendritic spine density in cultured hippocampal neurons. The opposite is observed for a genetic removal of Eps8. In early stage hippocampal culture neurons (DIV 4) Overexpressed Eps8 inhibits axonal filopldia formation and Netrin-1-induced axonal terminal protrusions. These results suggest that Eps8 plays an important role in regulating neuronal structural plasticity.
| Identifer | oai:union.ndltd.org:TW/098NCKU5550017 |
| Date | January 2010 |
| Creators | Wei-FangHuang, 黃微芳 |
| 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 | 69 |
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