Zhao Liangcai, Dong Minjian, Wang Dan, Ren Mengqian, Zheng Yongquan, Zheng Hong, Li Chen, Gao Hongchang
School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.
Department of Pharmacy, Women's Hospital, Medicine of School, Zhejiang University, Hangzhou, China.
Front Cell Neurosci. 2018 Jul 17;12:207. doi: 10.3389/fncel.2018.00207. eCollection 2018.
Cognitive dysfunction is a central nervous system (CNS) complication of diabetes mellitus (DM) that is characterized by impaired memory and cognitive ability. An in-depth understanding of metabolic alterations in the brain associated with DM will facilitate our understanding of the pathogenesis of cognitive dysfunction. The present study used an culture of primary neurons in a high-glucose (HG) environment to investigate characteristic alterations in neuron metabolism using nuclear magnetic resonance (NMR)-based metabonomics. High performance liquid chromatography (HPLC) was also used to measure changes in the adenosine phosphate levels in the hippocampal regions of streptozotocin (STZ)-induced diabetic rats. Our results revealed significant elevations in phosphocholine and ATP production in neurons and decreased formate, nicotinamide adenine dinucleotide (NAD), tyrosine, methionine, acetate and phenylalanine levels after HG treatment. However, the significant changes in lactate, glutamate, taurine and myo-inositol levels in astrocytes we defined previously in astrocytes, were not found in neurons, suggested cell-specific metabolic alterations. We also confirmed an astrocyte-neuron lactate shuttle between different compartments in the brain under HG conditions, which was accompanied by abnormal acetate transport. These alterations reveal specific information on the metabolite levels and transport processes related to neurons under diabetic conditions. Our findings contribute to the understanding of the metabolic alterations and underlying pathogenesis of cognitive decline in diabetic patients.
认知功能障碍是糖尿病（DM）的一种中枢神经系统（CNS）并发症，其特征为记忆力和认知能力受损。深入了解与糖尿病相关的大脑代谢改变将有助于我们理解认知功能障碍的发病机制。本研究利用高糖（HG）环境中原代神经元的培养，采用基于核磁共振（NMR）的代谢组学来研究神经元代谢的特征性改变。还使用高效液相色谱（HPLC）来测量链脲佐菌素（STZ）诱导的糖尿病大鼠海马区磷酸腺苷水平的变化。我们的结果显示，HG处理后神经元中的磷酸胆碱和ATP生成显著升高，而甲酸、烟酰胺腺嘌呤二核苷酸（NAD）、酪氨酸、蛋氨酸、乙酸盐和苯丙氨酸水平降低。然而，我们之前在星形胶质细胞中定义的星形胶质细胞中乳酸、谷氨酸、牛磺酸和肌醇水平的显著变化在神经元中未发现，提示存在细胞特异性代谢改变。我们还证实了在HG条件下大脑不同区域间存在星形胶质细胞 - 神经元乳酸穿梭，同时伴有乙酸盐转运异常。这些改变揭示了糖尿病条件下与神经元相关的代谢物水平和转运过程的特定信息。我们的研究结果有助于理解糖尿病患者认知功能下降的代谢改变和潜在发病机制。
