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Metabonomics reveals peripheral and central short-chain fatty acid and amino acid dysfunction in a naturally occurring depressive model of macaques

Authors Deng F, Pan J, Zheng P, Xia J, Yin B, Liang W, Li Y, Wu J, Xu F, Wu Q, Qu C, Li W, Wang H, Xie P

Received 1 September 2018

Accepted for publication 14 February 2019

Published 1 May 2019 Volume 2019:15 Pages 1077—1088

DOI https://doi.org/10.2147/NDT.S186071

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Prof. Dr. Roumen Kirov

Peer reviewer comments 2

Editor who approved publication: Dr Jun Chen


Feng-Li Deng,1–4,* Jun-Xi Pan,2,3,5,* Peng Zheng,2,3,6 Jin-Jun Xia,2,3 Bang-Min Yin,1–3 Wei-Wei Liang,1–3 Yi-Fan Li,2,3,6 Jing Wu,2,3 Fan Xu,2,3 Qing-Yuan Wu,2,3,7 Chao-Hua Qu,2,3 Wei Li,2,3 Hai-Yang Wang,2,3 Peng Xie1–3

1
Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, People’s Republic of China; 2Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China; 3Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 4School of Public Health and Management, Chongqing Medical University, Chongqing 400016, People’s Republic of China; 5The First Affiliated Hospital of Kunming Medical University, Kunming 650032, People’s Republic of China; 6Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China; 7Department of Neurology, Three Gorges Central Hospital, Chongqing Medical University, Chongqing 400016, People’s Republic of China

*These authors contributed equally to this work

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.

Keywords: naturally occurring depressive, depression, non-human primate, metabonomics, cerebrospinal fluid, short-chain fatty acid

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