Backround

Both type 2 diabetes (T2D) and Alzheimer’s disease affect large number of people all over the world, especially in developed countries, and involve common molecular mechanisms in degenerative processes.

Aim

Our study is to investigate the expression levels of the ADAMTS4, TIMP3, RELN, and BCAN genes which encode extracellular matrix molecules and are thought to be related to the pathophysiology of Alzheimer’s disease in rats that we used to develop a T2D model by injection of a streptozotocin (STZ) and feeding with high-fat diet (HFD).

Material and methods

In total, 40 rats were divided into four groups: HFD + STZ (10), HFD (10), STZ (10), and the control (10). The weight and blood glucose levels of all rats were recorded, and the insulin tolerance test was performed. At the end of the experimental period, the hippocampus of the rats was isolated and a part of this was used for gene expression analysis through real-time PCR, whereas other parts were used for histological analyses.

Results

Our results show that plaque-like structures were found in the histological examination of the experimental T2D model. In molecular studies, the expression levels of the ADAMTS4, TIMP3, RELN, and BCAN genes were decreased in the HFD +STZ and STZ groups compared with the control, whereas the same expression levels, except that of inhibitor TIMP3, were found to increase in the HFD group.

Conclusion

These genes encoding proteases that regulate neuronal activity have decreased levels in the T2D model. There may be potential in the adoption of new treatment approaches for Alzheimer’s and T2D.

中文翻译：

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实验性糖尿病模型大鼠海马中与阿尔茨海默氏病相关的细胞外基质基因的研究

背景

2型糖尿病（T2D）和阿尔茨海默氏病都影响着全世界的许多人，尤其是在发达国家，并且它们在退化过程中涉及共同的分子机制。

目标

我们的研究旨在调查ADAMTS4，TIMP3，RELN和BCAN基因的表达水平，这些基因编码细胞外基质分子，并被认为与大鼠阿尔茨海默氏病的病理生理学有关，我们曾经通过注射这种蛋白来建立T2D模型链脲佐菌素（STZ）和高脂饮食（HFD）喂养。

材料与方法

总共40只大鼠分为四组：HFD + STZ（10），HFD（10），STZ（10）和对照组（10）。记录所有大鼠的体重和血糖水平，并进行胰岛素耐受性测试。在实验期结束时，分离大鼠海马，其中一部分用于通过实时PCR进行基因表达分析，而其他部分用于组织学分析。

结果

我们的结果表明，在实验性T2D模型的组织学检查中发现了斑块状结构。在分子研究中，与对照组相比，HFD + STZ和STZ组中ADAMTS4，TIMP3，RELN和BCAN基因的表达水平降低，而除抑制剂TIMP3外，相同的表达水平有所增加。 HFD组。

结论

这些编码调节神经元活性的蛋白酶的基因在T2D模型中具有降低的水平。阿尔茨海默氏病和T2D可能会采用新的治疗方法。