Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, 20-090 Lublin, Poland.
Int J Mol Sci. 2021 Apr 9;22(8):3878. doi: 10.3390/ijms22083878.
The brain is the most vulnerable organ to glucose fluctuations, as well as inflammation. Considering that cognitive impairment might occur at the early stage of diabetes, it is very important to identify key markers of early neuronal dysfunction. Our overall goal was to identify neuroinflammatory and molecular indicators of early cognitive impairment in diabetic mice. To confirm cognitive impairment in diabetic mice, series of behavioral tests were conducted. The markers related to cognitive decline were classified into the following two groups: Neuroinflammatory markers: IL-1, IL-6, tumor necrosis factor- (TNF-) and genetic markers (, , ) which were estimated in brain regions. Our studies showed a strong association between hyperglycemia, hyperinsulinemia, neuroinflammation, and cognitive dysfunction in T2DM mice model. Cognitive impairment recorded in diabetes mice were associated not only with increased levels of cytokines but also decreased and mRNA expression level in brain regions associated with learning process and memory formation. The results of our research show that these indicators may be useful to test new forms of treatment of early cognitive dysfunction associated not only with diabetes but other diseases manifesting this type of disorders. The significant changes in and gene expression in early stage diabetes create opportunities it possible to use them to track the progression of CNS dysfunction and also to differential disease diagnosis running with cognitive impairment.
大脑是对葡萄糖波动以及炎症最敏感的器官。考虑到认知障碍可能发生在糖尿病的早期阶段，因此确定早期神经元功能障碍的关键标志物非常重要。我们的总体目标是确定糖尿病小鼠中神经炎症和早期认知障碍的分子标志物。为了确认糖尿病小鼠的认知障碍，我们进行了一系列行为测试。与认知能力下降相关的标志物分为以下两组：神经炎症标志物：IL-1、IL-6、肿瘤坏死因子- (TNF-) 和遗传标志物 (、、)，这些标志物在大脑区域中进行了评估。我们的研究表明，T2DM 小鼠模型中的高血糖、高胰岛素血症、神经炎症和认知功能障碍之间存在很强的相关性。在糖尿病小鼠中记录的认知障碍不仅与细胞因子水平升高有关，而且与与学习过程和记忆形成相关的大脑区域中的 和 mRNA 表达水平降低有关。我们研究的结果表明，这些指标可能有助于测试与糖尿病相关的早期认知功能障碍以及其他表现出这种类型障碍的疾病的新形式的治疗方法。在糖尿病的早期阶段， 和 基因表达的显著变化为使用它们来跟踪中枢神经系统功能障碍的进展以及对认知障碍进行差异化疾病诊断提供了机会。
