{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:01:59Z","timestamp":1787065319533,"version":"build-2736575974"},"reference-count":28,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T00:00:00Z","timestamp":1755734400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The development of new drugs for Alzheimer\u2019s disease (AD) remains a major challenge due to the disorder\u2019s complex and multifactorial nature. 2\u2032-Fucosyllactose (2\u2032-FL), a human milk oligosaccharide, has demonstrated promising neuroprotective properties. However, its effects on AD-related cognitive decline are not yet fully understood. This study aimed to investigate the therapeutic potential of 2\u2032-FL in an aging mouse model of AD and to explore the underlying mechanisms involved.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      5xFAD transgenic mice were treated with 2\u2032-FL and assessed for cognitive function using the Morris water maze and Y-maze tests. Immunohistochemical staining was used to evaluate amyloid-beta (A\u03b2) and phosphorylated tau (p-tau) levels in brain tissue samples. Blood samples were analyzed to determine circulating cytokine levels. Additionally, BV2 microglial cells and primary hippocampal neurons (PHNs) were used\n                      <jats:italic>in vitro<\/jats:italic>\n                      to investigate the effects of 2\u2032-FL on neuroinflammation, oxidative stress, and synaptic plasticity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>2\u2032-FL (300\u20131,200\u00a0mg\/kg, oral) improved cognitive performance in 5xFAD mice by shortening escape latency in the water maze and restoring alternation behavior in the Y-maze test. It significantly reduced A\u03b2 plaque load in the hippocampus and cortex but did not significantly affect tau hyperphosphorylation. Furthermore, 2\u2032-FL lowered plasma tumor necrosis factor (TNF)-\u03b1 and interleukin (IL)-6 levels. In BV2 cells, it suppressed d-galactose-induced neuroinflammation by downregulating TNF-\u03b1 and IL-6, and nuclear factor-\u03baB signaling. In PHNs, 2\u2032-FL reduced oxidative stress, restored mitochondrial function, and limited DNA damage. Additionally, it counteracted d-galactose-induced synaptic deficits by promoting neurite outgrowth, enhancing synaptic vesicle recycling, and upregulating the synaptic markers brain-derived neurotrophic factor, postsynaptic density protein-95, and synaptic vesicle protein 2.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      2\u2032-FL improved cognitive performance in 5xFAD mice, reduced A\u03b2 plaque deposition and pro-inflammatory cytokine levels\n                      <jats:italic>in vivo<\/jats:italic>\n                      , and mitigated oxidative stress and synaptic dysfunction in cellular models. These findings indicate that 2\u2032-FL modulates multiple pathological features relevant to AD in preclinical models.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1598030","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T05:28:01Z","timestamp":1755754081000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["2\u2032-Fucosyllactose mitigates cognitive deficits in Alzheimer models: targeting amyloid pathology, oxidative stress, and synaptic plasticity"],"prefix":"10.3389","volume":"16","author":[{"given":"Yeasmin Akter","family":"Munni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khoa Nguyen","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seon-Min","family":"Jeon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meeyul","family":"Hwang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Won","family":"Yoon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Young-Ha","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tae Woo","family":"Oh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sang Il","family":"Gum","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"In-Jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,21]]},"reference":[{"key":"B1","unstructured":"Medications for memory, cognition and dementia-related behaviors\n          \n          \n          2025"},{"key":"B2","unstructured":"Dementia statistics\n          \n          \n          2025"},{"key":"B3","doi-asserted-by":"publisher","first-page":"11757","DOI":"10.3390\/ijms241411757","article-title":"The molecular mechanisms of neuroinflammation in Alzheimer's disease, the consequence of neural cell death","volume":"24","author":"Choi","year":"2023","journal-title":"Int. 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