The neurogenic effects of rosmarinic acid in a mouse model of type 2 diabetes mellitus

There is emerging evidence for a dysregulation of insulin signaling in the brains of patients with Alzheimer’s disease (AD) with overlapping molecular features to Type 2 Diabetes Mellitus (T2DM). In addition, T2DM is a known risk factor of AD. The goal of this study was to investigate the neurogenic and neuroprotective potential of rosmarinic acid (RA) in a streptozotocin (STZ)-induced combined with high fat diet (HFD) mouse model of diabetes. Animals were divided into four experimental groups (control, diabetic, diabetic + RA, RA only). Behavioral analysis was performed to assess spatial learning and anxiety levels of animals, whereas quantitative real time PCR was carried out to assess the gene expression levels of neuronal markers of neurogenesis (Ki67, DCX and NeuN). A significant decrease in memory and spatial learning was observed in the diabetic mice, which was substantially improved by RA treatment. RA also increased the gene expression of NeuN, DCX and Ki67, which were dysregulated in the diabetic model. This study proposes RA as a potential therapeutic agent to mitigate neuronal dysfunction associated with T2DM by promoting adult hippocampal neurogenesis.

现有新兴证据表明，阿尔茨海默病（Alzheimer’s disease, AD）患者大脑内的胰岛素信号通路存在失调情况，其分子特征与2型糖尿病（Type 2 Diabetes Mellitus, T2DM）高度重叠。此外，2型糖尿病是已被证实的阿尔茨海默病风险因素。本研究旨在探究迷迭香酸（rosmarinic acid, RA）在链脲佐菌素（streptozotocin, STZ）联合高脂饮食（high fat diet, HFD）诱导的糖尿病小鼠模型中的神经发生与神经保护潜力。实验动物被分为4个实验组：对照组、糖尿病模型组、糖尿病+RA干预组以及单纯RA给药组。研究通过行为学分析评估动物的空间学习能力与焦虑水平，同时采用实时定量聚合酶链反应（quantitative real time PCR）检测神经发生相关神经元标志物（Ki67、DCX及NeuN）的基因表达水平。结果显示，糖尿病小鼠的记忆与空间学习能力显著下降，而RA干预可显著改善这一功能缺陷。此外，RA还可上调糖尿病模型中表达失调的NeuN、DCX及Ki67基因的表达水平。本研究提出，迷迭香酸可通过促进成年海马神经发生，作为潜在治疗剂缓解与2型糖尿病相关的神经元功能障碍。