Faculty Collaboration Database

Estradiol-induced enhancement of object memory consolidation involves hippocampal extracellular signal-regulated kinase activation and membrane-bound estrogen receptors. J Neurosci 2008 Aug 27;28(35):8660-7

Date

08/30/2008

Pubmed ID

18753366

Pubmed Central ID

PMC2693006

DOI

10.1523/JNEUROSCI.1968-08.2008

Scopus ID

2-s2.0-52049126390 (requires institutional sign-in at Scopus site)   237 Citations

Abstract

The extracellular signal-regulated kinase (ERK) pathway is critical for various forms of learning and memory, and is activated by the potent estrogen 17beta-estradiol (E(2)). Here, we asked whether E(2) modulates memory via ERK activation and putative membrane-bound estrogen receptors (ERs). Using ovariectomized mice, we first demonstrate that intraperitoneal injection of 0.2 mg/kg E(2) significantly increases dorsal hippocampal levels of phosphorylated ERK protein 1 h after injection. Second, we show that E(2) administered intraperitoneally (0.2 mg/kg) or via intrahippocampal infusion (5.0 microg/side) immediately after training in an object recognition task significantly enhances memory retention, and that the beneficial effect of intraperitoneal E(2) is blocked by dorsal hippocampal inhibition of ERK activation. Third, using bovine serum albumin-conjugated 17beta-estradiol (BSA-E(2)), we demonstrate that E(2) binding at membrane-bound ERs can increase dorsal hippocampal ERK activation and enhance object memory consolidation in an ERK-dependent manner. Fourth, we show that this effect is independent of nuclear ERs, but is dependent on the dorsal hippocampus. By demonstrating that E(2) enhances memory consolidation via dorsal hippocampal ERK activation, this study is the first to identify a specific molecular pathway by which E(2) modulates memory and to demonstrate a novel role for membrane-bound ERs in mediating E(2)-induced improvements in hippocampal memory consolidation.

Author List

Fernandez SM, Lewis MC, Pechenino AS, Harburger LL, Orr PT, Gresack JE, Schafe GE, Frick KM

Author

Karyn Frick BA,MA,PhD Professor in the Psychology department at University of Wisconsin - Milwaukee

MESH terms used to index this publication - Major topics in bold

Aminoacetonitrile
Analysis of Variance
Animals
Behavior, Animal
Choice Behavior
Drug Administration Routes
Enzyme Inhibitors
Estradiol
Estrogens
Exploratory Behavior
Extracellular Signal-Regulated MAP Kinases
Female
Hippocampus
Maze Learning
Mice
Mice, Inbred C57BL
Muscimol
Ovariectomy
Receptors, Estrogen
Time Factors