Metabonomics reveals peripheral and central short-chain fatty acid and amino acid dysfunction in a naturally occurring depressive model of macaques
Metabonomics reveals peripheral and central short-chain fatty acid and amino acid dysfunction in a naturally occurring depressive model of macaques
复制标题
代谢组学揭示了猕猴自然抑郁模型中的外周和中枢短链脂肪酸和氨基酸功能障碍
DOI：
10.2147/ndt.s186071
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发表时间：
2019-01-01
影响因子：
3.2
通讯作者：
Xie, Peng
中科院分区：
文献类型：
--
作者：
Deng, Feng-Li;Pan, Jun-Xi;Xie, Peng
目的：抑郁症是一种复杂的精神障碍。不同的抑郁动物模型通常基于不同的发病机制。材料和方法：利用我们先前在非人灵长类动物(食蟹猴，猕猴)上建立的自然发生抑郁(NOD)模型，我们对NOD雌性猕猴(N=10)和年龄和性别匹配的健康对照组(HCS)(N=12)的脑脊液(CSF)进行了代谢组学分析。用多元统计分析确定两组间差异表达的代谢物。应用独创性通路分析和代谢分析进行预测通路和生物功能分析。结果：共鉴定出37种代谢产物。NOD猕猴的主要特征是脂肪酸生物合成、ABC转运系统和氨基酸代谢(如天冬氨酸、甘氨酸、丝氨酸和苏氨酸代谢)的紊乱。有趣的是，我们还在NOD猕猴的血清中发现了8种短链脂肪酸和氨基酸的变化代谢物(每组13只)。结论：我们的发现提示外周和中枢短链脂肪酸和氨基酸参与了抑郁症的发病。
Purpose: Depression is a complex psychiatric disorder. Various depressive rodent models are usually constructed based on different pathogenesis hypotheses.Materials and methods: Herein, using our previously established naturally occurring depressive (NOD) model in a non-human primate (cynomolgus monkey, Macaca fascularis), we performed metabolomics analysis of cerebrospinal fluid (CSF) from NOD female macaques (N=10) and age-and gender-matched healthy controls (HCs) (N=12). Multivariate statistical analysis was used to identify the differentially expressed metabolites between the two groups. Ingenuity Pathways Analysis and MetaboAnalyst were applied for predicted pathways and biological functions analysis.Results: Totally, 37 metabolites responsible for discriminating the two groups were identified. The NOD macaques were mainly characterized by perturbations of fatty acid biosynthesis, ABC transport system, and amino acid metabolism (eg, aspartate, glycine, serine, and threonine metabolism). Interestingly, we found that eight altered CSF metabolites belonging to short-chain fatty acids and amino acids were also observed in the serum of NOD macaques (N=13 per group).Conclusion: Our findings suggest that peripheral and central short-chain fatty acids and amino acids are implicated in the onset of depression.