Neuroprotective Effects of Zinc Sulfate Against Type 2 Diabetes-Induced Encephalopathy in Aged Rats

This study investigates the neuroprotective effects of zinc sulfate (ZnSO<inf>4</inf>) 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 ZnSO<inf>4</inf> 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 ZnSO<inf>4</inf> significantly ameliorated systemic dyslipidemia. In the diabetic hippocampus, ZnSO<inf>4</inf> mitigated oxidative stress by decreasing MDA and elevating depleted GSH levels. Molecularly, ZnSO<inf>4</inf> upregulated the suppressed expressions of SIRT-1, GLUT3, BDNF, and Bcl-2, while downregulating pro-apoptotic Bax. Histopathological and immunohistochemical findings confirmed that ZnSO<inf>4</inf> reduced neuronal degeneration and vascular pathologies (PAS positivity), preserving neuroplasticity (elevated GAP43 and NGF) in both brain regions. In conclusion, ZnSO<inf>4</inf> 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.