The effects of 17[beta]-estradiol on the activty-regulated cytoskeleton associated protein (Arc), implicated in the consolidation of memory

Abstract

Activity-regulated cytoskeleton associated protein (Arc) is known to be induced by synaptic plasticity following memory consolidation. Since estrogen has been shown to play an important role in synaptogenesis, a key aspect of the synaptic plasticity, this study aimed to demonstrate the effects of estrogen on Arc expression and synaptic plasticity. This was indicated by an increase in postsynaptic density-95 (PSD-95) and synaptophysin (SYP) expression in SH--SY5Y cells. Using quantitative real-time PCR, Western blot, and immunocytochemistry techniques, the results showed that estrogen rapidly increased Arc mRNA and protein expression in SH--SY5Y cells. Estrogen-activated Arc expression was mediated via both estrogen receptor (ERβ), mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase (PI-3K), but not via protein kinase C (PKC) and Rho-associated kinase (ROCK). Moreover, in the present study, ERβ expression on membrane and cytoplasm of SH-SY5Y cells under normal conditions strongly supported the idea that estrogen-induced Arc is nongenomic action. On the other hand, prolonged estrogen treatment (more than 2 h) also enhanced synaptic plasticity in SH-SY5Y cells by an increase in PSD-95 and SYP expression. Moreover, the progression increased ERβ in the nucleus and decreased it in the membrane and in cytosol simultaneously. This occurred at the late phase of estrogen treatment, suggesting that these events were related to an increase in the novel synthesis of PSD-95 and SYP. These findings indicated a translocation mechanism of genomic estrogenic action. In addition, findings suggested that PI-3K inhibitor partially suppressed estrogen-enhanced PSD-95 and SYP expression, which is the crosstalk of classical genomic and nongenomic action on synaptic plasticity. In conclusion, the present study demonstrated the underlying mechanism of estrogen enhanced synaptic plasticity and memory consolidation regulating Arc, PSD-95, and SYP