Sporadic Alzheimer's disease (sAD) is the most common type of dementia and progressive neurodegenerative disease. To establish the sAD model, intracerebroventricular (ICV) streptozotocin (STZ) at a dose of 3 mg/kg was administered bilaterally in rats on a stereotaxic apparatus. Behavioral tests such as Morris water maze (MWM), novel object recognition (NOR) and open field test were performed to evaluate cognitive and locomotor functions. Two treatment doses (5 mg/kg and 10 mg/kg) of sodium orthovanadate (SOV) and rivastigmine (2 mg/kg) were given orally to ICV-STZ induced rats for 21 days. Cortical and hippocampal tissues were dissected. Estimation of oxidative stress, mitochondrial dysfunction as complex I, II, III, IV activity, cholinergic function as acetylcholinesterase activity, ELISA for phosphorylated tau protein and insulin degrading enzyme (IDE), neuroinflammation as NF-κB gene expression and insulin signaling functioning as Q-RT-PCR for IR, IRS-1, PI3K, AKT, GSK-3β gene expression were performed. Behavioral results with SOV and rivastigmine treatment revealed decreased escape latency and increased discrimination index in MWM and NOR respectively. Treatment results with SOV also demonstrated attenuation of oxidative imbalance, improved mitochondrial activity, and reversed IDE and tau pathology. SOV treatment upregulated gene expression of IR, IRS-1, PI3K, and AKT, and downregulated that of GSK-3β. SOV results were compared with standard drug rivastigmine. Conclusively, the memory enhancement by SOV was mediated through oxidative balance, mitochondrial enzyme complex activation, and improved insulin signaling regulation. However, the primary mechanism of SOV remained attenuation of tau pathology by the upregulation of IRS-1/PI3K/AKT/GSK-3β pathway and reversal of insulin resistance in terms of IDE. Hence, in sAD paradigm, SOV contributed to memory improvement evident with the findings of behavioral studies, which can further potentially have clinical significance in AD.

散发性阿尔茨海默病 (sAD) 是最常见的痴呆类型和进行性神经退行性疾病。为了建立 sAD 模型，在立体定位仪上对大鼠双侧脑室内 (ICV) 链脲佐菌素 (STZ) 给药，剂量为 3 mg/kg。进行了莫里斯水迷宫 (MWM)、新物体识别 (NOR) 和旷场测试等行为测试，以评估认知和运动功能。向 ICV-STZ 诱导的大鼠口服给予两种治疗剂量（5 毫克/千克和 10 毫克/千克）的原钒酸钠 (SOV) 和利凡斯的明（2 毫克/千克），持续 21 天。解剖皮质和海马组织。估计氧化应激、线粒体功能障碍作为复合物 I、II、III、IV 活性，胆碱能功能作为乙酰胆碱酯酶活性，进行了磷酸化 tau 蛋白和胰岛素降解酶 (IDE) 的 ELISA、神经炎症作为 NF-κB 基因表达和胰岛素信号传导作为 Q-RT-PCR 用于 IR、IRS-1、PI3K、AKT、GSK-3β 基因表达。SOV 和利凡斯的明治疗的行为结果分别显示 MWM 和 NOR 的逃逸潜伏期减少和鉴别指数增加。SOV 的治疗结果还证明了氧化失衡的减弱、线粒体活性的改善以及 IDE 和 tau 病理学的逆转。SOV 处理上调 IR、IRS-1、PI3K 和 AKT 的基因表达，并下调 GSK-3β 的基因表达。SOV 结果与标准药物利凡斯的明进行了比较。总之，SOV 的记忆增强是通过氧化平衡、线粒体酶复合物激活、并改善胰岛素信号调节。然而，SOV 的主要机制仍然是通过上调 IRS-1/PI3K/AKT/GSK-3β 通路来减弱 tau 病理，并在 IDE 方面逆转胰岛素抵抗。因此，在 sAD 范式中，SOV 有助于记忆改善，行为研究的结果很明显，这可能进一步对 AD 具有临床意义。