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Neuropharmacology

Neuropharmacology

IF: 4.6
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Hippocampal O-GlcNAc homeostasis sustains memory reconsolidation amidst stress hormone exposure

Published:1 July 2025 DOI: 10.1016/j.neuropharm.2025.110582
Chenran Wang , Jianhui Wang , Feng Liu , Jingying Liu , Yan Huang , Mengting Xia , Hexi Yang , Zhiyong Xiao , Wenxia Zhou

Abstract

Memory is not always reliable, inherently malleable. The malleability enables organisms to adapt their behavior based on future predictions, increasing survival odds. O-linked β-N-acetylglucosamine (O-GlcNAc) has emerged as a modulator of memory, notwithstanding, its impact on memory malleability remains to be comprehensively elucidated. Here, we report that the reliable prediction-mediated strengthening or incomplete reminder-mediated updating of original memories, a process called reconsolidation can alter memory malleability, which is impaired in mice (C57BL/6J, males) under stress. Pharmacologically enhancing O-GlcNAc levels afford dynamic and phase-specific protection of reconsolidation. Meanwhile, overexpression of hippocampal O-GlcNAc transferase (OGT), aimed at elevating O-GlcNAc, recapitulated this protective effect. Inhibiting OGT substrate availability negates this protective effect. Interestingly, the concurrent overexpression of hippocampal OGT alongside substrate supplementation, intended to excessively elevate O-GlcNAc, proves ineffective in affording additional protection. It even triggers a reappearance of reconsolidation resistance in the original memory. This protective role of O-GlcNAc, seemingly acting in a buffering-like manner, insulating reconsolidation from aberrant modifications within an optimal range. These data establish hippocampal O-GlcNAc as a potential target for preserving memory malleability.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
Thiamet G Discontinued 1009816-48-1 C9H16N2O4S 162 suppliers $30.00-$4950.00
Thiamet G Discontinued 1009816-48-1 C9H16N2O4S 162 suppliers $30.00-$4950.00
Thiamet G Discontinued 1009816-48-1 C9H16N2O4S 162 suppliers $30.00-$4950.00
Thiamet G Discontinued 1009816-48-1 C9H16N2O4S 162 suppliers $30.00-$4950.00

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