L-fucose administration ameliorates chronic social defeat stress-induced depressive-like behaviors by restoring GDP-fucose biosynthetic activation and core fucosylation

Description

Zheng and co-authors report in this 2026 mouse study that a simple sugar, L-fucose, eases depression-like behavior caused by chronic social stress. The team used the chronic social defeat model. In that model, mice are repeatedly bullied by aggressive cage mates. They traced the damage to a sugar-processing pathway in the hippocampus, a brain region central to mood and memory.

Stressed mice showed depressive-like behavior, brain inflammation, and lost synaptic proteins needed for neuron signaling. Stress had lowered levels of GDP-fucose, the activated sugar form used in a protein-tagging process called core fucosylation, by suppressing two enzymes that make it. Feeding L-fucose restored both enzymes, calmed inflammation, and rebuilt synaptic proteins. Blocking the tagging process with a drug instead made stressed mice worse, and L-fucose also quieted inflammation in the colon, hinting at a gut-brain connection.

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Source: https://europepmc.org/article/MED/PMC13468815