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Translational stroke research
08, 2020;11 (4): 734-746.

The Involvement of Canonical Wnt Signaling in Memory Impairment Induced by Chronic Cerebral Hypoperfusion in Mice.

Min-Soo Kim, Jihye Bang, Won Kyung Jeon
Author Information
  1. Min-Soo Kim: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, South Korea.
  2. Jihye Bang: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, South Korea.
  3. Won Kyung Jeon: Herbal Medicine Research Division, Korea Institute of Oriental Medicine, Daejeon, 34054, South Korea. wkjeon@kiom.re.kr.
PMID: 31960287 DOI: 10.1007/s12975-019-00748-1

Abstract

Chronic cerebral hypoperfusion (CCH) has been proposed to contribute to the progression of memory loss, which is the main symptom of vascular cognitive impairment (VCI). Accumulating evidence indicates that underlying pathophysiology, such as neurodegeneration, may lead to memory loss. However, the underlying molecular basis of memory loss in CCH remains unclear. Here, we investigated the roles of canonical Wnt signaling, which modulates hippocampal function, in a CCH model. CCH was induced by unilateral common carotid artery occlusion (UCCAO). Mice were randomly divided into a sham-operated group or one of three UCCAO groups with different endpoints (1.5, 2.5, and 3.5 months) after UCCAO. Memory function and hippocampal levels of Wnt-related proteins were measured. A Wnt activator, lithium, was administered intraperitoneally to assess memory improvements. In the groups examined 2.5 and 3.5 months after UCCAO, impaired object recognition memory was accompanied by inhibition of Wnt signaling and decreased expression of synaptic/neural activity-related proteins. Recognition memory and Wnt signaling were significantly positive correlated. Moreover, activation of Wnt signaling with lithium significantly attenuated memory loss and recovered synaptic/neural marker expression after UCCAO. Our results suggest that CCH may affect synaptic plasticity via dysregulation of signaling pathways, including canonical Wnt signaling, which could be partly involved in memory loss. As Wnt activator administration alleviated the effects of CCH on memory loss, modulation of Wnt signaling may be a promising therapeutic strategy for VCI.

Keywords

Chronic cerebral hypoperfusion Unilateral common carotid artery occlusion Vascular cognitive impairment Wnt signaling

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MeSH Term

Animals
Cerebrovascular Circulation
Cerebrovascular Disorders
Cognitive Dysfunction
Hippocampus
Lithium
Male
Memory
Memory Disorders
Mice, Inbred C57BL
Wnt Signaling Pathway

Chemicals

Lithium
Journal Article Research Support, Non-U.S. Gov't

Word Cloud

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