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Neuropsychiatric Disease and Treatment Volume 15, 2019 - Issue
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Original Research

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

Feng-Li Deng1 Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, People’s Republic of China, [email protected];2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected];4 School of Public Health and Management, Chongqing Medical University, Chongqing 400016, People’s Republic of China
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Jun-Xi Pan2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected];5 The First Affiliated Hospital of Kunming Medical University, Kunming 650032, People’s Republic of China
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Peng Zheng2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected];6 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China
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Jin-Jun Xia2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected]
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Bang-Min Yin1 Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, People’s Republic of China, [email protected];2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected]
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Wei-Wei Liang1 Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, People’s Republic of China, [email protected];2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected]
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Yi-Fan Li2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected];6 Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People’s Republic of China
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Jing Wu2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected]
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Fan Xu2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected]
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Qing-Yuan Wu2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected];7 Department of Neurology, Three Gorges Central Hospital, Chongqing Medical University, Chongqing 400016, People’s Republic of China
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Chao-Hua Qu2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected]
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Wei Li2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected]
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Hai-Yang Wang2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected]
&
Peng Xie1 Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, People’s Republic of China, [email protected];2 Chongqing Key Laboratory of Neurobiology, Chongqing 400016, People’s Republic of China, [email protected];3 Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, People’s Republic of China, [email protected]Correspondence[email protected]
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Pages 1077-1088 | Published online: 01 May 2019

Figures & data

Figure 1 Behavioral observation of the cynomolgus monkeys. (A) Cynomolgus monkeys in a realistic social context. (B) Slumped or collapsed posture of a NOD macaque (red arrow). (C) A CON macaque. (D) The significant differential behavioral results between NOD macaques (n=10) and CON macaques (n=12).

Note: *Behaviors of greater duration in healthy controls relative to NOD macaques.
Abbreviations: CON, control; NOD, naturally occurring depressive; HC, healthy control.
Figure 1 Behavioral observation of the cynomolgus monkeys. (A) Cynomolgus monkeys in a realistic social context. (B) Slumped or collapsed posture of a NOD macaque (red arrow). (C) A CON macaque. (D) The significant differential behavioral results between NOD macaques (n=10) and CON macaques (n=12).

Table 1 Basic background data of NOD and CON macaques

Figure 2 An overview of the GC-MS-based metabonomic workflow identifying differentially expressed CSF metabolites in NOD macaques.

Note: *The data was from our published work (Xu et alCitation16).
Abbreviations: CON, control; NOD, naturally occurring depressive; GC-MS, gas chromatography–mass spectrometry; CSF, cerebrospinal fluid; VIP, variable importance in the projection; IPA, Ingenuity Pathways Analysis.
Figure 2 An overview of the GC-MS-based metabonomic workflow identifying differentially expressed CSF metabolites in NOD macaques.

Figure 3 (A) Representative GC–MS total ion chromatograms (TIC) of the CON and NOD group. (B) Partial least squares-discriminate analysis (PLS-DA) scores plot derived from GC–MS spectra of the CON and NOD macaques.

Abbreviations: CON, control; NOD, naturally occurring depressive; GC–MS, gas chromatography–mass spectrometry.
Figure 3 (A) Representative GC–MS total ion chromatograms (TIC) of the CON and NOD group. (B) Partial least squares-discriminate analysis (PLS-DA) scores plot derived from GC–MS spectra of the CON and NOD macaques.

Figure 4 (A) Heat map of differentially expressed CSF metabolites in CON and NOD macaques. (B) Chemical taxonomy and (C) cellular locations based on the annotations of Human Metabolome Database (HMDB). The predicted biological functions were significantly involved in the biosynthesis of lipid (D) and uptake of amino acids (E).

Abbreviations: CON, control; NOD, naturally occurring depressive; CSF, cerebrospinal fluid.
Figure 4 (A) Heat map of differentially expressed CSF metabolites in CON and NOD macaques. (B) Chemical taxonomy and (C) cellular locations based on the annotations of Human Metabolome Database (HMDB). The predicted biological functions were significantly involved in the biosynthesis of lipid (D) and uptake of amino acids (E).

Table 2 Differential metabolites of cerebrospinal fluid (CSF) between NOD and CON macaques

Table 3 Top five affected ingenuity canonical pathways enriched in CSF between NOD and CON macaques

Figure 5 Network analysis of differentially expressed metabolites in CSF and serum of NOD macaques.

Notes: *The data was from our published work (Xu et alCitation16). Red-colored boxes and red-colored lines indicate upregulation in NOD macaques compared with control (CON), while green-colored boxes and green-colored lines indicate downregulation. The width of the line represents the VIP scores of differential metabolites.
Abbreviations: NOD, naturally occurring depressive; CSF, cerebrospinal fluid; VIP, variable importance in the projection.
Figure 5 Network analysis of differentially expressed metabolites in CSF and serum of NOD macaques.

Table S1 The included behaviors of 12 behavior categories

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