Dickkopf-1 Blocks 17β-estradiol-enhanced Object Memory Consolidation in Ovariectomized Female Mice

Abstract

The memory-enhancing effects of 17β-estradiol (E2) are dependent upon rapid activation of several cell signaling cascades within the dorsal hippocampus (DH). Among many cell-signaling pathways that mediate memory processes, Wnt/β-catenin signaling has emerged as a potential key player. However, whether E2 interacts with Wnt/β-catenin signaling to promote memory consolidation is unknown. Therefore, the present study examined whether Wnt/β-catenin signaling within the DH is necessary for E2-induced memory consolidation in both object recognition and object placement tasks. Here, ovariectomized mice received immediate post-training infusions of E2 or vehicle into the dorsal third ventricle plus the endogenous Wnt/β-catenin antagonist Dickkopf-1 (Dkk-1) or vehicle into the dorsal hippocampus to assess whether the memory-enhancing effects of E2 depend on activation of Wnt/β-catenin signaling. Our results suggest that Dkk-1 blocks E2-induced memory enhancement as hypothesized, but may operate in an unexpected manner by only moderately blunting Wnt/β-catenin signaling while concurrently activating Wnt/JNK signaling. The current study provides novel insight into the mechanisms by which E2 enhances memory consolidation in the DH, as well as critical information about the mechanistic actions of Dkk-1.