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BDNF via tropomyosin receptor kinase B (TrkB) exerts neuroprotection by activating protein kinase B (Akt) to inhibit glycogen synthase kinase\u20103\u03b2 (GSK3\u03b2). Although Vitamin D3 (VitD3) has demonstrated favorable metabolic and neuronal outcomes in MetS, the precise molecular mechanisms underlying its neuroprotective effects remain poorly elucidated. We aimed to test the hypothesis that VitD3 mitigates MetS\u2010induced cognition deficits and neuropathic pain via modulating the BDNF\/TRKB\/Akt\/GS3K\u03b2 signaling pathway. MetS was induced in male rats by 10% fructose\u2010supplemented water and 3% salt\u2010enriched diet. After 6 weeks, normal and MetS rats received either vehicle or VitD3 (10\u2009\u00b5g\/kg\/day) for an additional 6 weeks. Glycemic status, lipid profile, and behavioral changes were assessed. The advanced glycation end products (AGEs), and markers of inflammation (TNF\u2010\u03b1 and NF\u2010\u03baB), oxidative stress (malondialdehyde), and apoptosis (caspase3), as well as BDNF, TrkB, PI3K, Akt, GSK3\u03b2, phosphorylated tau, and amyloid beta (A\u03b2) were assessed in the cerebral cortex. MetS rats had deteriorated glycemic and lipid profiles, higher AGEs, reduced levels of BDNF, TrkB, PI3K, and active Akt, along with increased GSK3\u03b2 levels, inflammation, oxidative stress, and apoptosis. These changes were associated with higher levels of cognitive impairment markers phosphorylated tau and A\u03b2, as well as behavioral changes indicative of cognitive impairment and neuropathic pain. VitD3 improved the cognitive and behavioral alterations, while mitigating the associated molecular derangements. Our results indicate that VitD3 may exert neuroprotective effects by modulating the BDNF\/TrkB\/PI3K\/Akt\/GSK3\u03b2 signaling pathway.<\/jats:p>","DOI":"10.1002\/jbt.70082","type":"journal-article","created":{"date-parts":[[2024,12,9]],"date-time":"2024-12-09T06:31:13Z","timestamp":1733725873000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["RETRACTED: Vitamin D3 Exerts a Neuroprotective Effect in Metabolic Syndrome Rats: Role of BDNF\/TRKB\/Akt\/GS3K\u03b2 Pathway"],"prefix":"10.1002","volume":"38","author":[{"given":"Noha","family":"Aladdin","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Zagazig University Zagazig Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salah A.","family":"Ghareib","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy Zagazig University Zagazig 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