{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T13:29:25Z","timestamp":1791293365834,"version":"4.1.0"},"reference-count":43,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T00:00:00Z","timestamp":1751500800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Baotou City Health Commission Science and Technology Plan Project","award":["wsjkkj2022109"],"award-info":[{"award-number":["wsjkkj2022109"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec020\">\n<jats:title>Background<\/jats:title>\n<jats:p>Type 2 diabetes mellitus (T2DM) is associated with cognitive dysfunction, which significantly impacts the quality of life. Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has shown potential neuroprotective effects. This study investigates the efficacy of semaglutide in ameliorating cognitive dysfunction in a mouse model of T2DM.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec021\">\n<jats:title>Methods<\/jats:title>\n<jats:p>Male C57BL\/6J mice were fed a high-fat diet for four weeks and received a single intraperitoneal injection of streptozotocin (150\u2009mg\/kg) to induce T2DM. All mice were divided into four groups: control, diabetes control (T2DM), semaglutide treatment (semaglutide, 0.1\u2009mg\/kg) and dapagliflozin treatment (dapagliflozin 1\u2009mg\/kg). Cognitive function was assessed using the Morris water maze (MWM) test. Histomorphological analysis of hippocampal tissues was performed using H&amp;E and Nissl staining. Immunofluorescence was used to assess LRP1 expression and apoptosis. Biochemical analyses measured oxidative stress markers (SOD, MDA) and inflammatory cytokines (IL-1\u03b2, IL-6, TNF-\u03b1, CRP).<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec022\">\n<jats:title>Results<\/jats:title>\n<jats:p>Semaglutide treatment significantly reduced blood glucose levels in diabetic mice. In the MWM test, semaglutide-treated mice showed reduced escape latencies, indicating improved spatial learning and memory. Histomorphological analysis revealed preserved neuronal structure in the hippocampus with reduced neuronal damage and apoptosis in the semaglutide-treated group. Immunofluorescence showed increased LRP1 expression and decreased apoptosis. Biochemical analyses indicated that semaglutide reduced oxidative stress and inflammatory markers, further supporting its neuroprotective effects.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec023\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>Semaglutide effectively ameliorates cognitive dysfunction in T2DM mice, likely through mechanisms involving the reduction of oxidative stress, inflammation, and neuronal apoptosis. These findings suggest that semaglutide has potential as a therapeutic agent for managing diabetes-associated cognitive decline. Further research, including long-term studies and clinical trials, is necessary to validate these findings and explore the broader applicability of semaglutide in treating cognitive impairments in diabetic patients.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0326897","type":"journal-article","created":{"date-parts":[[2025,7,3]],"date-time":"2025-07-03T17:43:20Z","timestamp":1751564600000},"page":"e0326897","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":14,"title":["Semaglutide ameliorates diabetes-associated cognitive dysfunction in mouse model of type 2 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