Sex Differences in the Rapid Cell Signaling Mechanisms Underlying the Memory-Enhancing Effects of 17β-Estradiol. eNeuro 2018;5(5)
Date
11/09/2018Pubmed ID
30406188Pubmed Central ID
PMC6220582DOI
10.1523/ENEURO.0267-18.2018Scopus ID
2-s2.0-85056254216 (requires institutional sign-in at Scopus site) 46 CitationsAbstract
Little is known about how 17β-estradiol (E2) mediates memory formation in males. In ovariectomized (OVX) mice, bilateral dorsal hippocampal (DH) infusion of E2 enhances memory consolidation in object recognition (OR) and object placement (OP) tasks in a manner dependent on activation of extracellular signal-regulated kinase (ERK) and Akt signaling. Here, bilateral DH E2 infusion enhanced memory consolidation in both tasks among OVX female, gonadally-intact male, and castrated male mice, suggesting comparable facilitation of memory consolidation in both sexes, independent of testicular hormones in males. Contrary to previous reports in OVX mice, E2 did not increase DH ERK or Akt phosphorylation in males, nor did the ERK inhibitor U0126 [1,4-diamino-2,3-dicyano-1,4-bis (o-aminophenylmercapto) butadiene] prevent E2 from enhancing memory consolidation among intact and castrated males. These data suggest that ERK activation is not necessary for E2 to enhance memory consolidation in males, and compared with previous reports in females, reveal novel sex differences in the cell-signaling pathways through which E2 facilitates memory consolidation. To explore the mechanisms underlying E2-induced memory enhancements in males, phosphorylation of the transcription factor cAMP response element binding protein (CREB) in the DH was assessed. E2 increased phospho-CREB levels in both sexes, yet U0126 did not block these increases in castrated or intact males, indicating that E2 regulates CREB phosphorylation in males via an ERK-independent mechanism. Collectively, these findings suggest that the beneficial effects of hippocampal E2 on memory consolidation in males and females are mediated by different molecular mechanisms, which has important implications for the development of treatments to reduce memory dysfunction in men and women.
Author List
Koss WA, Haertel JM, Philippi SM, Frick KMAuthor
Karyn Frick BA,MA,PhD Professor in the Psychology department at University of Wisconsin - MilwaukeeMESH terms used to index this publication - Major topics in bold
AnimalsEstradiol
Estrogens
Female
Hippocampus
Male
Memory
Memory Consolidation
Mice
Sex Characteristics
Signal Transduction
