Estrogen stimulates activity-regulated cytoskeleton associated protein (Arc) expression via the MAPK- and PI-3K-dependent pathways in SH-SY5Y cells

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, we aimed to study the effects of estrogen on Arc expression in SH-SY5Y human neuroblastoma cells. Using quantitative real-time PCR, Western blot, and confocal immunocytochemistry techniques we found that estrogen markedly increased Arc mRNA and protein expression in SH-SY5Y cells. Estrogen-activated Arc expression was mediated via mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase (PI-3K), but not protein kinase C (PKC) and Rho-associated kinase (ROCK), and in the estrogen receptor (ER)-dependent manner. Estrogen also significantly upregulated the dendritic spine scaffolding protein, postsynaptic density-95 (PSD-95), as well as expression of the presynaptic vesicle protein, synaptophysin. Our findings demonstrate the possible mechanisms of estrogen-induced synaptic plasticity, as well as memory consolidation.