{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:27:49Z","timestamp":1787138869641,"version":"build-2736575974"},"reference-count":36,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>This study investigates the neuroprotective effects of zinc sulfate (ZnSO4) against diabetic encephalopathy in an aged female rat model of Type 2 diabetes mellitus (T2DM). T2DM was induced using a 4-week high-fat diet followed by a single 25 mg\/kg STZ injection. Diabetic rats were treated with 10 mg\/kg\/day ZnSO4 for 4 weeks. We evaluated serum lipids, hippocampal oxidative stress (MDA, GSH), gene expressions (SIRT-1, GLUT3, BDNF, Bax, Bcl-2), and structural injuries (Nissl, PAS, GAP43, NGF) in the hippocampus and cerebral cortex. Results demonstrated that ZnSO4 significantly ameliorated systemic dyslipidemia. In the diabetic hippocampus, ZnSO4 mitigated oxidative stress by decreasing MDA and elevating depleted GSH levels. Molecularly, ZnSO4 upregulated the suppressed expressions of SIRT-1, GLUT3, BDNF, and Bcl-2, while downregulating pro-apoptotic Bax. Histopathological and immunohistochemical findings confirmed that ZnSO4 reduced neuronal degeneration and vascular pathologies (PAS positivity), preserving neuroplasticity (elevated GAP43 and NGF) in both brain regions. In conclusion, ZnSO4 supplementation provides potent, multifaceted neuroprotection against T2DM-associated neurodegeneration by regulating systemic dyslipidemia, restoring redox homeostasis, activating the SIRT-1\/BDNF anti-apoptotic pathway, and preserving structural integrity.<\/jats:p>","DOI":"10.3390\/ijms27167412","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:04:12Z","timestamp":1787137452000},"page":"7412","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Neuroprotective Effects of Zinc Sulfate Against Type 2 Diabetes-Induced Encephalopathy in Aged Rats"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4816-830X","authenticated-orcid":false,"given":"Omer","family":"Unal","sequence":"first","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Samsun University, Samsun 55080, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7750-482X","authenticated-orcid":false,"given":"Nilufer","family":"Akgun-Unal","sequence":"additional","affiliation":[{"name":"Department of Biophysics, Faculty of Medicine, Ondokuz Mayis University, Samsun 55270, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emre Soner","family":"Tiryaki","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Ondokuz Mayis University, Samsun 55139, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cemile","family":"Avci-Akan","sequence":"additional","affiliation":[{"name":"Department of Transport Services, Ala\u00e7am Vocational School of Higher Education, Ondokuz May\u0131s University, Samsun 55800, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2391-2152","authenticated-orcid":false,"given":"Elif","family":"Gulbahce-Mutlu","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, Faculty of Medicine, KTO Karatay University, Konya 42020, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adem","family":"Atacak","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Selcuk University, Konya 42130, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulkerim Kasim","family":"Baltaci","sequence":"additional","affiliation":[{"name":"Department of Physiology, Faculty of Medicine, Selcuk University, Konya 42130, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1038\/s41574-025-01114-y","article-title":"Insulin resistance in type 2 diabetes mellitus","volume":"21","author":"Accili","year":"2025","journal-title":"Nat. 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