Estradiol Induces Dose-, Time-, and Region-Specific Changes to Activity-Regulated Cytoskeleton-Associated Protein (Arc) in the Mouse Brain

Estrogens have been implicated extensively in learning, memory, dendritic spinogenesis, and synaptic plasticity. The molecular pathways underlying estrogens’ rapid, nongenomic actions are not well understood, however protein translation of dendritically-localized mRNA transcripts may be a possible mechanism of action. The Activity-regulated cytoskeleton-association protein (Arc) has emerged as a strong candidate for the mediation of these effects. Here, we present findings from mouse in vivo and primary cortical cell culture models demonstrating Arc’s dynamic regulation following stimulation by 17beta-estradiol (E2) within 15- to 40-minutes of treatment. Further, we show that E2 induces a differential localization of dendritic Arc dependent on the length of time that follows E2 treatment. In sum, these data suggest a novel role for Arc acting within a mechanism of E2-facilitated neuronal actions that is dose-, time-, and dendritic region-dependent, advocating for a multi-mechanism approach to studying Arc’s involvement in estrogenic short-term memory facilitation within the mouse brain.