Alzheimer's disease (AD) is prevalent in old age people and is one of the most common brain diseases. Brain insulin resistance, neuroinflammation, oxidative stress, and mitochondrial and cholinergic dysfunction are key features of the disease. In our study, streptozotocin (STZ) in a dose of 3 mg/kg was injected in male Wistar rats bilaterally through the intracerebroventricular (ICV) route on stereotaxic apparatus. Chromium picolinate (CrPic) was tested at doses of 1 mg/kg, 2 mg/kg, and 4 mg/kg, while rivastigmine (2 mg/kg) was used as reference standard drug. Cognitive dysfunction induced by STZ was assessed by behavioral tests like Morris water maze and novel object recognition test. Treatment with CrPic revealed attenuation of cognitive deficit. This was confirmed by behavioral tests, biochemical estimations of antioxidant enzymes, oxidative stress, nitrosative stress, and cholinergic and mitochondrial activity. CrPic did not change AchE activity significantly. STZ-induced neuroinflammation evident by increased TNF-α, IL-6, and CRP levels was also significantly decreased by CrPic. Dysfunctional insulin signaling after ICV-STZ was demonstrated by reduced IRS-1, PI3K, AKT, BDNF gene expression, and increased GSK-3β, NF-κB gene expression with the help of qRT-PCR. CrPic treatment produced an improvement in insulin signaling revealed by increased gene expression of IRS-1, PI3-K, AKT, BDNF, and decreased gene expression of GSK-3β and NF-κB. It was concluded that CrPic reversed AD pathology revealed by improved memory, reduced oxidative stress, neuroinflammation, mitochondrial dysfunction, and upregulated insulin signaling.

中文翻译：

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吡啶甲酸铬通过靶向神经炎症和IRS-1 / PI3K / AKT /GSK-3β途径减轻散发性阿尔茨海默氏样痴呆的ICV-STZ大鼠范型的认知功能障碍

阿尔茨海默氏病（AD）在老年人中很普遍，是最常见的脑部疾病之一。脑胰岛素抵抗，神经炎症，氧化应激以及线粒体和胆碱能功能障碍是该疾病的关键特征。在我们的研究中，以3 mg / kg剂量的链脲佐菌素（STZ）通过立体定位仪上的脑室内（ICV）途径向雄性Wistar大鼠双侧注射。分别以1 mg / kg，2 mg / kg和4 mg / kg的剂量测试了吡啶甲酸铬（CrPic），而使用卡巴拉汀（2 mg / kg）作为参考标准药物。STZ诱发的认知功能障碍通过行为测试（如莫里斯水迷宫和新颖的物体识别测试）进行评估。CrPic治疗可减轻认知功能障碍。行为测试，抗氧化酶的生化评估，氧化应激，亚硝化应激以及胆碱能和线粒体活性。CrPic没有显着改变AchE活性。CrPic还可显着降低TNF-α，IL-6和CRP水平所引起的STZ诱导的神经炎症。借助qRT-PCR，通过减少IRS-1，PI3K，AKT，BDNF基因表达，以及增加GSK-3β，NF-κB基因表达，证明了ICV-STZ后胰岛素功能异常。CrPic处理可改善IRS-1，PI3-K，AKT，BDNF的基因表达，并降低GSK-3β和NF-κB的基因表达，从而改善胰岛素信号传导。结论是，CrPic可通过改善记忆力，降低氧化应激，神经炎症，线粒体功能障碍和上调胰岛素信号传导来逆转AD病理。以及胆碱能和线粒体活性。CrPic没有显着改变AchE活性。CrPic还可以显着降低TNF-α，IL-6和CRP水平引起的STZ诱导的神经炎症。借助qRT-PCR，通过减少IRS-1，PI3K，AKT，BDNF基因表达，以及增加GSK-3β，NF-κB基因表达，证明了ICV-STZ后胰岛素功能异常。CrPic处理可改善IRS-1，PI3-K，AKT，BDNF的基因表达，并降低GSK-3β和NF-κB的基因表达，从而改善胰岛素信号传导。结论是，CrPic可通过改善记忆力，降低氧化应激，神经炎症，线粒体功能障碍和上调胰岛素信号传导来逆转AD病理。以及胆碱能和线粒体活性。CrPic没有显着改变AchE活性。CrPic还可显着降低TNF-α，IL-6和CRP水平所引起的STZ诱导的神经炎症。借助qRT-PCR，通过减少IRS-1，PI3K，AKT，BDNF基因表达，以及增加GSK-3β，NF-κB基因表达，证明了ICV-STZ后胰岛素功能异常。CrPic处理可改善IRS-1，PI3-K，AKT，BDNF的基因表达，并降低GSK-3β和NF-κB的基因表达，从而改善胰岛素信号传导。结论是，CrPic可通过改善记忆力，降低氧化应激，神经炎症，线粒体功能障碍和上调胰岛素信号传导来逆转AD病理。CrPic还可显着降低TNF-α，IL-6和CRP水平所引起的STZ诱导的神经炎症。借助qRT-PCR，通过减少IRS-1，PI3K，AKT，BDNF基因表达，以及增加GSK-3β，NF-κB基因表达，证明了ICV-STZ后胰岛素功能异常。CrPic处理可改善IRS-1，PI3-K，AKT，BDNF的基因表达，并降低GSK-3β和NF-κB的基因表达，从而改善胰岛素信号传导。结论是，CrPic可通过改善记忆力，降低氧化应激，神经炎症，线粒体功能障碍和上调胰岛素信号传导来逆转AD病理。CrPic还可显着降低TNF-α，IL-6和CRP水平所引起的STZ诱导的神经炎症。借助qRT-PCR，通过减少IRS-1，PI3K，AKT，BDNF基因表达，以及增加GSK-3β，NF-κB基因表达，证明了ICV-STZ后胰岛素功能异常。CrPic处理可改善IRS-1，PI3-K，AKT，BDNF的基因表达，并降低GSK-3β和NF-κB的基因表达，从而改善胰岛素信号传导。结论是，CrPic可通过改善记忆力，降低氧化应激，神经炎症，线粒体功能障碍和上调胰岛素信号传导来逆转AD病理。借助qRT-PCR，BDNF基因表达增加，而GSK-3β，NF-κB基因表达增加。CrPic处理可改善IRS-1，PI3-K，AKT，BDNF的基因表达，并降低GSK-3β和NF-κB的基因表达，从而改善胰岛素信号传导。结论是，CrPic可通过改善记忆力，降低氧化应激，神经炎症，线粒体功能障碍和上调胰岛素信号传导来逆转AD病理。借助qRT-PCR可以检测BDNF基因表达，并增加GSK-3β，NF-κB基因表达。CrPic处理可改善IRS-1，PI3-K，AKT，BDNF的基因表达，并降低GSK-3β和NF-κB的基因表达，从而改善胰岛素信号传导。结论是，CrPic可通过改善记忆力，降低氧化应激，神经炎症，线粒体功能障碍和上调胰岛素信号传导来逆转AD病理。