Interestingly, estrogen–increased pERK is ERs–dependent pathway, suggesting that estrogen promotes neuronal survival likely through a membrane–associated ER–mediated rapid signaling cascade (Zhao and Brinton 2007). In addition to neuroprotection, recent study showed that estrogen signaled through the MAPK pathway to induce phosphorylated cAMP response element binding (pCREB) (Lee et al. 2004). Because CREB has been linked to estrogen induction of excitatory synaptic formation, this study suggested that estrogen may enhance synaptic plasticity via MAPK activation (Lee et al. 2004). Moreover, estrogen–enhanced hippocampal memory consolidation was mediated MAPK signaling pathway by increasing pERK (Fernandez et al. 2008).