在中樞神經系統發育時期，神經細胞特有的結構及突觸可塑性，是神經細胞彼此連結形成的基礎，甚至成熟腦部的學習與記憶也需要這樣的機制來協助高等神經的認知功能建構。Epidermal receptor substrate 8 (Eps8) 已知存在細胞質內的生長因子基質 (growth factor substrates) ，用以活化細胞膜上表皮生長因子 EGF (epidermal growth factor) 受體，經下游訊息傳遞路徑，驅使Eps8去調節細胞骨架組成的主要蛋白質—肌動蛋白 (actin) 的聚合。
近年來研究發現，在Eps8基因踢除小鼠，對乙醇引起的神經興奮及急性酒醉反應的副作用具有耐受性，並且該小鼠相較控制組正常小鼠對乙醇的攝取量明顯增加。除此之外在該小鼠小腦的單極梳狀細胞 (unipolar brush cells) 發現有密集的Eps8蛋白質表現，在顆粒細胞 (granule cells) 上則是中量的表現。然而截至目前為止Eps8在海馬迴中如何表現，以及所扮演的角色和功能仍是未明。
在本研究中發現Eps8此蛋白質在大鼠海馬迴表現量較高的時期，約在大鼠出生後7~28天，而此時期已知是活體內神經發育突觸形成 (synaptogenesis) 重要的時期。此外，在出生後第14天大鼠海馬迴中分離出的神經突觸小體 (synaptosomes) ，以及突觸後小體 (synaptoneurosomes) 皆有Eps8的高量表現在其中。在體外培養的海馬迴神經元中，過量表現Eps8基因能明顯增加樹突上突觸小刺 (spine) 的密度，而抑制Eps8基因後的神經元中則呈現相反的結果。在海馬迴神經元發育早期 (DIV 4) ，過量表現 Eps8則抑制了軸突絲狀偽足的形成和Netrin-1所誘導的軸突末端小突起的動態變化。因此本研究發現Eps8在調節海馬迴神經的結構可塑性上，可能扮演重要的角色。

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.

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