Estradiol-Mediated Spine Changes in the Dorsal Hippocampus and Medial Prefrontal Cortex of Ovariectomized Female Mice Depend on ERK and mTOR Activation in the Dorsal Hippocampus

• DOI: 10.1523/jneurosci.3135-15.2016
• Publication Date: 2016-02-03T17:10:37Z
• Authors: Jennifer J. Tuscher; Victoria Luine; Maya Frankfurt; Karyn M. Frick
• Keywords: Estradiol; MAP Kinase Signaling System; Dendritic Spines; Ovariectomy; TOR Serine-Threonine Kinases; Prefrontal Cortex; Hippocampus; Mice, Inbred C57BL; Mice; 03 medical and health sciences; 0302 clinical medicine; Animals; Female

Dendritic spine plasticity underlies the formation and maintenance of memories. Both natural fluctuations systemic administration 17β-estradiol (E2) alter density in dorsal hippocampus (DH) rodents. DH E2 infusion enhances hippocampal-dependent memory by rapidly activating extracellular signal-regulated kinase (ERK)-dependent signaling mammalian target rapamycin (mTOR), a key protein synthesis pathway involved remodeling. Here, we investigated whether directly into drives changes other brain regions, identified cell-signaling pathways that mediate these effects. significantly increased basal apical on CA1 pyramidal neurons 30 min 2 h after infusion. also medial prefrontal cortex (mPFC) later, suggesting E2-mediated activity mPFC spinogenesis. The increase observed intracerebroventricular was blocked an ERK or mTOR inhibitor. did not affect dentate gyrus ventromedial hypothalamus, specific effects mPFC. Collectively, data demonstrate treatment elicits ERK- mTOR-dependent spinogenesis neurons, may support memory-enhancing E2.Although systemically injected increases dendritic density, molecular mechanisms regulating E2-induced vivo are largely unknown. We found infused later. Surprisingly, (mPFC), estrogenic regulation influences Moreover, inhibition activation prevented from increasing spines, demonstrating is necessary for These findings provide novel insights through which mediates