{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:01:04Z","timestamp":1785391264075,"version":"3.55.0"},"reference-count":77,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T00:00:00Z","timestamp":1785369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23K27133, 24K09817, 25K09941"],"award-info":[{"award-number":["23K27133, 24K09817, 25K09941"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>\n                    Chronic psychosocial stress is a major driver of depression, yet the glycometabolic mechanisms linking stress exposure to neuroinflammation and synaptic dysfunction remain poorly understood. Here, using a chronic social defeat stress (CSDS) model, we demonstrated that L-fucose supplementation markedly attenuated depressive-like behaviors and suppressed neuroinflammation in the hippocampus. L-fucose also reduced Iba1-positive microglial accumulation, inhibited JAK2\/STAT3 inflammatory signaling, and restored the stress-induced loss of synaptic proteins, including \u03b1-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunits and postsynaptic density protein 95 (PSD95). Mechanistically, CSDS downregulated hippocampal guanosine 5\u2032-diphosphate (GDP)-fucose levels, thereby impairing core fucosylation. This defect was associated with downregulation of key enzymes in the GDP-fucose salvage biosynthetic pathway, including fucokinase (FUK) and fucose-1-phosphate guanylyltransferase (FPGT), both of which were restored by L-fucose administration. Consistently, pharmacological inhibition of fucosylation with 2-fluorofucose (2FF) suppressed GDP-fucose and\n                    <jats:italic>Fuk<\/jats:italic>\n                    expression, thereby exacerbating depressive-like behaviors and neuroinflammation in the CSDS model. Furthermore, L-fucose or MF30 alleviated CSDS-induced inflammatory responses in distal colon tissues. Taken together, this study clearly identifies a link between GDP-fucose synthesis and chronic stress and, for the first time, shows that alterations in key enzymes in the GDP-fucose salvage pathway play critical roles in CSDS-induced depressive-like behaviors and\u00a0neuroinflammation, suggesting that restoring GDP-fucose biosynthetic activation may offer a promising therapeutic strategy for stress-related neuropsychiatric disorders.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2026.1909378","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T05:38:34Z","timestamp":1785389914000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["L-fucose administration ameliorates chronic social defeat stress-induced depressive-like behaviors by restoring GDP-fucose biosynthetic activation and core fucosylation"],"prefix":"10.3389","volume":"17","author":[{"given":"Meng","family":"Zheng","sequence":"first","affiliation":[{"name":"Division of Regulatory Glycobiology, Graduate School of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University","place":["Sendai, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomohiko","family":"Fukuda","sequence":"additional","affiliation":[{"name":"Division of Regulatory Glycobiology, Graduate School of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University","place":["Sendai, Japan"]},{"name":"Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical and Pharmaceutical University","place":["Sendai, Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Division of Regulatory Glycobiology, Graduate School of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University","place":["Sendai, 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