Genomic and non-genomic actions of estrogen on synaptic plasticity in SH-SY5Y cells.

Estrogen modulates synaptic plasticity, an important mechanism of memory storage. Previously, we have reported that estrogen rapidly increases the expression of Arc (activity-regulated cytoskeleton associated protein), a key protein for synaptic plasticity, via non-genomic phosphoinositide-3 kinase (PI-3K)-, mitogen-activated protein kinase (MAPK)-, and estrogen receptor (ER)-dependent pathways in SH-SY5Y cells. The present study aimed to investigate the role of each ER subtype, alpha and beta, in synaptic plasticity in SH-SY5Y cells. The specific agonist of ER beta (DPN) markedly induced Arc expression that mimics treatment with estrogen, but not ER alpha (PTT). Determination of subcellular localization of ER beta using immunocytochemistry shows that ER beta was retained in the cytoplasm of the untreated cells. In estrogen-treated cells, the membrane and cytosolic ER beta gradually decreased, while nuclear ER beta progressively increased in time-dependent manner, suggesting estrogen-dependent nuclear translocation of ER beta. Nuclear accumulation of ER beta at 6-12h post-estrogen treatment, leads to increased PSD-95 and SYP mRNA expression, indicating the classical genomic estrogenic action on synaptic plasticity. However, the block of PI-3K signaling by Wortmannin partially suppressed estrogen (48 h)-induced PSD-95 and SYP expression, suggesting a crosstalk mechanism between genomic and non-genomic actions of estrogen on synaptic plasticity. Therefore, the estrogen-enhanced synaptic plasticity is ER beta-dependent and involves the crosstalk mechanism of non-genomic and genomic estrogenic actions. (c) 2009 Elsevier Ireland Ltd. All rights reserved.