title: Metabolomics identifies perturbations in amino acid metabolism in the prefrontal cortex of the learned helplessness rat model of depression.
abstract: Major depressive disorder is a serious psychiatric condition associated with high rates of suicide and is a leading cause of health burden worldwide. However, the underlying molecular mechanisms of major depression are still essentially unclear. In our study, a non-targeted gas chromatography-mass spectrometry-based metabolomics approach was used to investigate metabolic changes in the prefrontal cortex of the learned helplessness (LH) rat model of depression. Body-weight measurements and behavioral tests including the active escape test, sucrose preference test, forced swimming test, elevated plus-maze and open field test were used to assess changes in the behavioral spectrum after inescapable footshock stress. Rats in the stress group exhibited significant learned helpless and depression-like behaviors, while without any significant change in anxiety-like behaviors. Using multivariate and univariate statistical analysis, a total of 18 differential metabolites were identified after the footshock stress protocol. Ingenuity Pathways Analysis and MetaboAnalyst were applied for predicted pathways and biological functions analysis. "Amino Acid Metabolism, Molecule Transport, Small Molecule Biochemistry" was the most significantly altered network in the LH model. Amino acid metabolism, particularly glutamate metabolism, cysteine and methionine metabolism, arginine and proline metabolism, was significantly perturbed in the prefrontal cortex of LH rats.
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
authors.forename: Xinyu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Lanxiang
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Yuqing
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Juncai
authors.initials: J
authors.lastname: Pu
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Lining
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Chanjuan
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Yuan
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China.
authors.forename: Hanping
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurology and Psychiatry, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing, China. Electronic address: xiepeng973@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Xie
mesh_terms: D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000378:metabolism; D003865:Major Depressive Disorder / Q000378:metabolism*; D004195:Disease Models, Animal; D004597:Electroshock; D008401:Gas Chromatography-Mass Spectrometry; D006380:Helplessness, Learned; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D017397:Prefrontal Cortex / Q000378:metabolism*; D011897:Random Allocation; D017207:Rats, Sprague-Dawley
chemical_list: D000596:Amino Acids
keywords: depression; gas chromatography–mass spectrometry; learned helplessness; metabolomics; rat