Dickkopf-1 blocks 17β-estradiol-enhanced object memory consolidation in ovariectomized female mice
Year: 2019
Type: article
Abstract: The memory-enhancing effects of 17β-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/β-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/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 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/β-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/β-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/β-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. • The Wnt antagonist Dickkopf-1 (Dkk-1) impairs memory consolidation in males. • Here, Dkk-1 prevented 17β-estradiol (E 2 ) from enhancing memory in females. • E 2 and Dkk-1 may interact in a β-catenin-independent manner in the hippocampus. • The effects of Dkk-1 may include activation of Wnt/JNK signaling.
Source: Hormones and Behavior
Language: English
Topic: Memory and Neural Mechanisms
Subfield: Cognitive Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,150
OpenAlex ID: W2918916498