Estradiol-induced object memory consolidation in middle-aged female mice requires dorsal hippocampal extracellular signal-regulated kinase and phosphatidylinositol 3-kinase activation. J Neurosci 2010 Mar 24;30(12):4390-400
Date
03/26/2010Pubmed ID
20335475Pubmed Central ID
PMC2852263DOI
10.1523/JNEUROSCI.4333-09.2010Scopus ID
2-s2.0-77949837819 (requires institutional sign-in at Scopus site) 129 CitationsAbstract
We previously demonstrated that dorsal hippocampal extracellular signal-regulated kinase (ERK) activation is necessary for 17beta-estradiol (E(2)) to enhance novel object recognition in young ovariectomized mice (Fernandez et al., 2008). Here, we asked whether E(2) has similar memory-enhancing effects in middle-aged and aged ovariectomized mice, and whether these effects depend on ERK and phosphatidylinositol 3-kinase (PI3K)/Akt activation. We first demonstrated that intracerebroventricular or intrahippocampal E(2) infusion immediately after object recognition training enhanced memory consolidation in middle-aged, but not aged, females. The E(2)-induced enhancement in middle-aged females was blocked by intrahippocampal inhibition of ERK or PI3K activation. Intrahippocampal or intracerebroventricular E(2) infusion in middle-aged females increased phosphorylation of p42 ERK in the dorsal hippocampus 15 min, but not 5 min, after infusion, an effect that was blocked by intrahippocampal inhibition of ERK or PI3K activation. Dorsal hippocampal PI3K and Akt phosphorylation was increased 5 min after intrahippocampal or intracerebroventricular E(2) infusion in middle-aged, but not aged, females. Intracerebroventricular E(2) infusion also increased PI3K phosphorylation after 15 min, and this effect was blocked by intrahippocampal PI3K, but not ERK, inhibition. These data demonstrate for the first time that activation of dorsal hippocampal PI3K/Akt and ERK signaling pathways is necessary for E(2) to enhance object recognition memory in middle-aged females. They also reveal that similar dorsal hippocampal signaling pathways mediate E(2)-induced object recognition memory enhancement in young and middle-aged females and that the inability of E(2) to activate these pathways may underlie its failure to enhance object recognition in aged females.
Author List
Fan L, Zhao Z, Orr PT, Chambers CH, Lewis MC, 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
Age FactorsAnimals
Dose-Response Relationship, Drug
Drug Interactions
Enzyme Inhibitors
Estradiol
Estrogens
Exploratory Behavior
Extracellular Signal-Regulated MAP Kinases
Female
Hippocampus
Mice
Mice, Inbred C57BL
Ovariectomy
Phosphatidylinositol 3-Kinases
Phosphorylation
Statistics, Nonparametric
Time Factors
