PDF(Pubmed)
Abstract：
Alzheimer\'s disease (AD) is an increasingly important public health concern due to the increasing proportion of older individuals within the general population. The impairment of processes responsible for adequate brain energy supply primarily determines the early features of the aging process. Restricting brain energy supply results in brain hypometabolism prior to clinical symptoms and is anatomically and functionally associated with cognitive impairment. The present study investigated changes in metabolic profiles induced by intracerebroventricular-streptozotocin (ICV-STZ) in an AD-like animal model. To this end, male Wistar rats received a single injection of STZ (3 mg·kg-1) by ICV (2.5 μL into each ventricle for 5 min on each side). In the second week after receiving ICV-STZ, rats were tested for cognitive performance using the Morris Water Maze test and subsequently prepared for positron emission tomography (PET) to confirm AD-like symptoms. Tandem Mass Spectrometry (MS/MS) analysis was used to detect amino acid changes in cerebrospinal fluid (CFS) samples. Our metabolomics study revealed a reduction in the concentrations of various amino acids (alanine, arginine, aspartic acid, glutamic acid, glycine, isoleucine, methionine, phenylalanine, proline, serine, threonine, tryptophane, tyrosine, and valine) in CSF of ICV-STZ-treated animals as compared to controls rats. The results of the current study indicate amino acid levels could potentially be considered targets of nutritional and/or pharmacological interventions to interfere with AD progression.
摘要：
阿尔茨海默病（AD）是一个日益重要的公共卫生问题，因为老年人在普通人群中的比例越来越高。负责充足大脑能量供应的过程的损害主要决定了衰老过程的早期特征。限制脑能量供应导致临床症状之前的脑代谢减退,并且在解剖学和功能上与认知障碍相关。本研究调查了AD样动物模型中脑室内链脲佐菌素（ICV-STZ）诱导的代谢谱变化。为此,雄性Wistar大鼠接受ICV单次注射STZ（3mg·kg-1）（每个心室2.5μL，每侧5分钟）。在收到ICV-STZ后的第二周，使用Morris水迷宫试验测试大鼠的认知表现,随后准备用于正电子发射断层扫描(PET)以确认AD样症状。串联质谱(MS/MS)分析用于检测脑脊液(CFS)样品中的氨基酸变化。我们的代谢组学研究揭示了各种氨基酸（丙氨酸，精氨酸天冬氨酸,谷氨酸，甘氨酸,异亮氨酸,蛋氨酸,苯丙氨酸,脯氨酸,丝氨酸,苏氨酸,色氨酸,酪氨酸,和缬氨酸）与对照大鼠相比，在ICV-STZ处理的动物的CSF中。当前研究的结果表明，氨基酸水平可能被认为是营养和/或药理干预的目标，以干扰AD进展。
