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

The memory-enhancing effects of 17 beta-estradiol (E-2) 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/beta-catenin signaling has emerged as a potential key player because of its importance to hippocampal development and synaptic plasticity. However, whether E-2 interacts with Wnt/beta-catenin signaling to promote memory consolidation is unknown. Therefore, the present study examined whether Wnt/beta-catenin signaling within the DH is necessary for E-2-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 E-2 or vehicle into the dorsal third ventricle plus the endogenous Wnt/beta-catenin antagonist Dickkopf-1 (Dkk-1) or vehicle into the DH to assess whether the memory-enhancing effects of E-2 depend on activation of Wnt/beta catenin signaling. Our results suggest that Dkk-1 blocks E-2 induced memory enhancement as hypothesized, but may do so by only moderately blunting Wnt/beta-catenin signaling while concurrently activating Wnt/JNK signaling. The current study provides novel insights into the mechanisms through which E-2 enhances memory consolidation in the DH, as well as critical information about the mechanistic actions of Dkk-1.