Estrogens exert rapid effects on cognitive functions, particularly short-term memory, through non-genomic mechanisms within the brain. In ovariectomized (OVX) female mice, systemic or localized administration of 17-estradiol (E2) enhances short-term social recognition memory (SRM) within 40 minutes. This effect is accompanied by an increase in dendritic spine density in CA1 neurons of the dorsal hippocampus, suggesting a structural basis for enhanced memory formation. However, the precise molecular mechanisms underlying these rapid effects remain unclear. Estrogens are known to modulate actin cytoskeletal dynamics via actin polymerization and stimulate the translation of synaptic proteins, both of which are critical for synaptic plasticity and learning. To determine whether these processes are essential for E2-facilitated SRM, researchers investigated the roles of actin polymerization and protein synthesis using specific inhibitors.
In this study, OVX female mice were treated with either latrunculin A (LAT), an actin polymerization inhibitor, or anisomycin (ANI), a protein synthesis inhibitor, administered directly into the dorsal hippocampus prior to testing.CD64 Antibody Biological Activity The highest doses of LAT and ANI that did not impair baseline SRM were selected to avoid confounding effects on general behavior or motivation. These sub-effective doses were then used to assess their impact on E2-induced facilitation of SRM.241479-67-4 supplier Results showed that pre-treatment with LAT or ANI blocked the ability of E2 to enhance SRM, indicating that both actin polymerization and protein synthesis are necessary for the rapid memory-enhancing effects of E2.PMID:33759275 In contrast, inhibition of DNA transcription using actinomycin D had no effect on SRM, confirming that transcription-independent mechanisms underlie the rapid action of E2.
Further analysis revealed that E2 increased dendritic spine density in the stratum radiatum of the CA1 region within 15 minutes post-treatment. This increase was completely abolished by LAT but unaffected by ANI, indicating that actin polymerization is required for the morphological changes induced by E2, while protein synthesis is not. Interestingly, spine length was altered only in response to ANI treatment, suggesting that protein synthesis may influence spine maturation rather than initial formation. Moreover, when mice performed the SRM task, E2 failed to increase spine density at 40 minutes post-treatment, highlighting the transient nature of E2-induced structural changes. Task performance appeared to interfere with the persistence of these changes, possibly due to activity-dependent pruning or reorganization of synaptic connections.
These findings demonstrate that the rapid facilitation of short-term SRM by E2 depends on both actin polymerization and protein synthesis, although they serve distinct roles: actin remodeling supports immediate structural changes, while protein synthesis may be involved in downstream signaling or stabilization of new synapses. Importantly, the absence of effects from transcription inhibition underscores the non-genomic nature of E2’s rapid actions. Together, these results provide strong evidence that E2 rapidly enhances memory through dynamic alterations in the neuronal cytoskeleton and local protein translation, offering insights into the cellular mechanisms of hormonal modulation of cognition.MedChemExpress (MCE) offers a wide range of high-quality research chemicals and biochemicals (novel life-science reagents, reference compounds and natural compounds) for scientific use. We have professionally experienced and friendly staff to meet your needs. We are a competent and trustworthy partner for your research and scientific projects.Related websites: https://www.medchemexpress.com
