Metabolomic analysis reveals metabolic disturbances in the prefrontal cortex of the lipopolysaccharide-induced mouse model of depression.
Major depressive disorder (MDD) is a debilitating illness. However, the underlying molecular mechanisms of depression remain largely unknown. Increasing evidence supports that inflammatory cytokine disturbances may be associated with the pathophysiology of depression in humans. Systemic administration of lipopolysaccharide (LPS) has been used to study inflammation-associated neurobehavioral changes in rodents, but no metabonomic study has been conducted to assess differential metabolites in the prefrontal cortex (PFC) of a LPS-induced mouse model of depression. Here, we employed a gas chromatography-mass spectrometry-based metabonomic approach in the LPS-induced mouse model of depression to investigate any significant metabolic changes in the PFC. Multivariate statistical analysis, including principal component analysis (PCA), partial least squares-discriminate analysis (PLS-DA), and pair-wise orthogonal projections to latent structures discriminant analysis (OPLS-DA), was implemented to identify differential PFC metabolites between LPS-induced depressed mice and healthy controls. A total of 20 differential metabolites were identified. Compared with control mice, LPS-treated mice were characterized by six lower level metabolites and 14 higher level metabolites. These molecular changes were closely related to perturbations in neurotransmitter metabolism, energy metabolism, oxidative stress, and lipid metabolism, which might be evolved in the pathogenesis of MDD. These findings provide insight into the pathophysiological mechanisms underlying MDD and could be of valuable assistance in the clinical diagnosis of MDD.
Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Key Laboratory of Laboratory Medical Diagnostics of Education, Department of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China.
Yu
Y
Wu
Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
Yuying
Y
Fu
Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
Chenglong
C
Rao
Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Department of Pathology, Faculty of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
Wenwen
W
Li
Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, The Inner Mongolia Autonomous Region People's Hospital, Hohhot, Inner Mongolia 010017,China.
Zihong
Z
Liang
Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
Chanjuan
C
Zhou
Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Peng
P
Shen
Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
Pengfei
P
Cheng
Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China.
Li
L
Zeng
Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Dan
D
Zhu
Department of Neurology, Yongchuan Hospital of Chongqing Medical University, Chongqing 402460, China; Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China.
Libo
L
Zhao
Chongqing Key Laboratory of Neurobiology, Chongqing 400016, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China; Department of Neurology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: xiepeng58@21cn.com.
Peng
P
Xie
D000818:Animals; D001835:Body Weight / Q000502:physiology; D003863:Depression / Q000139:chemically induced* / Q000473:pathology*; D004195:Disease Models, Animal; D004435:Eating / Q000523:psychology; D005518:Food Preferences / Q000523:psychology; D008401:Gas Chromatography-Mass Spectrometry; D019417:Hindlimb Suspension; D008070:Lipopolysaccharides; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D051379:Mice; D008813:Mice, Inbred ICR; D017397:Prefrontal Cortex / Q000378:metabolism*; D025341:Principal Component Analysis; D013550:Swimming / Q000523:psychology
D008070:Lipopolysaccharides
Gas chromatography–mass spectrometry; Lipopolysaccharide; MDD; Major depressive disorder; Metabonomic; Prefrontal cortex