Behavioural brain research, 2019-05, Vol.364, p.50-61
2019
Volltextzugriff (PDF)
Details
- Autor(en) / Beteiligte
- Titel
- Hippocampus-specific Rictor knockdown inhibited 17β-estradiol induced neuronal plasticity and spatial memory improvement in ovariectomized mice
- Ist Teil von
- Behavioural brain research, 2019-05, Vol.364, p.50-61
- Ort / Verlag
- Netherlands: Elsevier B.V
- Erscheinungsjahr
- 2019
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- •Hippocampal Rictor was regulated by ovariectomy and E2 replacement.•siRictor inhibited E2 induced changes of spine density and synapse density.•siRictor inhibited E2 induced changes of actin remodeling and synaptic proteins.•siRictor inhibited E2 induced changes of spatial memory disorder caused by OVX.•Rictor might be the target against estrogen-related cognitive disorder.. Estrogens have been shown to play profound roles in the regulation of the structure and function of the hippocampus; however, the underlying mechanism is not clear. Previous studies have shown that when Rictor, the core component of the mammalian target of the rapamycin complex 2 (mTORC2), was deleted, hippocampal actin polymerization was reduced and long-term memory was seriously impaired. Although hippocampal Rictor could be regulated by estrogen receptor agonists/antagonists, whether Rictor could directly mediate estrogenic regulation of neuronal plasticity, spatial learning and memory remains unclear. In this study, we first examined the regulation of hippocampal Rictor and P-AKTser473 (P-AKT) by E2, then we used Rictor-specific dsRNA (shRictor) injected into the hippocampi of E2-treated ovariectomized (OVX) mice or into cultured cells. The results showed that both Rictor and P-AKT could be regulated by E2. OVX induced actin depolymerization, decreases in CA1 spine density and synapse density as well as changes in synaptic proteins were reversed by E2 replacement. However, these E2-mediated effects were significantly blocked by shRictor treatment. Similar results were also demonstrated by in vitro cell culture studies using E2 and/or shRictor. Importantly, we found that E2 replacement induced improvements in learning and memory impairment seen in OVX mice were significantly blocked by shRictor. Taken together, the current studies provided the first direct evidence for the important role of Rictor in estrogenic action on the hippocampus, indicating that it may be a therapeutic target for the treatment of E2-related, hippocampus-dependent cognitive dysfunction.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0166-4328eISSN: 1872-7549DOI: 10.1016/j.bbr.2019.02.014Titel-ID: cdi_proquest_miscellaneous_2183189008
- Format
- –
- Schlagworte
- Actin polymerization, Actins - metabolism, Animals, Estradiol - metabolism, Estradiol - pharmacology, Estrogen, Estrogens - metabolism, Estrogens - pharmacology, Female, Gene Knockdown Techniques - methods, Hippocampus, Hippocampus - metabolism, Mice, Mice, Inbred C57BL, mTORC2, Neuronal Plasticity - drug effects, Neuronal Plasticity - physiology, Oncogene Protein v-akt - metabolism, Ovariectomy, Rapamycin-Insensitive Companion of mTOR Protein - genetics, Rapamycin-Insensitive Companion of mTOR Protein - metabolism, Rictor, Spatial memory, Spatial Memory - physiology, Synapses - drug effects, Temporal Lobe - drug effects