Zheng Hong, Lin Qiuting, Wang Dan, Xu Pengtao, Zhao Liangcai, Hu Wenyi, Bai Guanghui, Yan Zhihan, Gao Hongchang
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, 325035, China.
Radiology Department of the Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, 325027, China.
Metab Brain Dis. 2017 Apr;32(2):585-593. doi: 10.1007/s11011-016-9949-0. Epub 2017 Jan 9.
Diabetes mellitus (DM) can result in cognitive dysfunction, but its potential metabolic mechanisms remain unclear. In the present study, we analyzed the metabolite profiling in eight different brain regions of the normal rats and the streptozotocin (STZ)-induced diabetic rats accompanied by cognitive dysfunction using a H NMR-based metabolomic approach. A mixed linear model analysis was performed to assess the effects of DM, brain region and their interaction on metabolic changes. We found that different brain regions in rats displayed significant metabolic differences. In addition, the hippocampus was more susceptible to DM compared with other brain regions in rats. More interestingly, significant interaction effects of DM and brain region were observed on alanine, creatine/creatine-phosphate, lactate, succinate, aspartate, glutamate, glutamine, γ-aminobutyric acid, glycine, choline, N-acetylaspartate, myo-inositol and taurine. Based on metabolic pathway analysis, we speculate that cognitive dysfunction in the STZ-induced diabetic rats may be associated with brain region-specific metabolic alterations involving energy metabolism, neurotransmitters, membrane metabolism and osmoregulation.
糖尿病（DM）可导致认知功能障碍，但其潜在的代谢机制仍不清楚。在本研究中，我们采用基于核磁共振氢谱的代谢组学方法，分析了正常大鼠和链脲佐菌素（STZ）诱导的伴有认知功能障碍的糖尿病大鼠八个不同脑区的代谢物谱。进行了混合线性模型分析，以评估糖尿病、脑区及其相互作用对代谢变化的影响。我们发现大鼠的不同脑区表现出显著的代谢差异。此外，与大鼠的其他脑区相比，海马体对糖尿病更敏感。更有趣的是，观察到糖尿病和脑区对丙氨酸、肌酸/磷酸肌酸、乳酸、琥珀酸、天冬氨酸、谷氨酸、谷氨酰胺、γ-氨基丁酸、甘氨酸、胆碱、N-乙酰天门冬氨酸、肌醇和牛磺酸有显著的相互作用效应。基于代谢途径分析，我们推测STZ诱导的糖尿病大鼠的认知功能障碍可能与涉及能量代谢、神经递质、膜代谢和渗透调节的脑区特异性代谢改变有关。
