Dickkopf-1 blocks 17β-estradiol-enhanced object memory consolidation in ovariectomized female mice.

The memory-enhancing effects of 17β-estradiol (E2) depend upon rapid activation of several cell-signaling cascades within the dorsal hippocampus (DH). Among the many cell-signaling pathways that mediate memory processes, Wnt/β-catenin signaling has emerged as a potential key player because of its importance to hippocampal development and synaptic plasticity. 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 ovariectomized mice tested in the object recognition and object placement tasks. Ovariectomized C57BL/6 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 DH 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 do so by only moderately blunting Wnt/β-catenin signaling while concurrently activating Wnt/JNK signaling. The current study provides novel insights into the mechanisms through which E2 enhances memory consolidation in the DH, as well as critical information about the mechanistic actions of Dkk-1.