Proteomic and metabolomic characterization of amygdala in chronic social defeat stress rats

Fan, Liancheng; Yang, Lining; Li, Xuemei; Teng, Teng; Xiang, Yajie; Liu, Xueer; Jiang, Yuanliang; Zhu, Yinglin; Xie, Peng

doi:10.1016/j.bbr.2021.113407

Cited by 12 publications

(14 citation statements)

References 71 publications

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“…73,74 Integrated analysis of proteomics and metabolomics indicated that, similar to other reports but different, significant differences were enriched in response to hydrogen peroxide, reactive oxygen species, acute inflammatory response, acute-phase response, regulation of leukocyte chemotaxis, lipid transport, and lipid localization. 75 This might be because the rat serum was employed for proteomics and metabolomics.…”

Section: Discussionmentioning

confidence: 99%

Human umbilical cord mesenchymal stem cells reverse depression in rats induced by chronic unpredictable mild stress combined with lipopolysaccharide

Wang,

Li,

Song

et al. 2024

CNS Neurosci Ther

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BackgroundInflammation and oxidative stress are considered crucial to the pathogenesis of depression. Rat models of depression can be created by combined treatments of chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS). Behaviors associated with depression could be improved by treatment with mesenchymal stem cells (MSCs) owing to immunomodulatory functions of the cells. Therapeutic potentials of the MSCs to reverse pro‐inflammatory cytokines, proteins, and metabolites were identified by transcriptomic, proteomic, and metabolomic analysis, respectively.MethodsA depression model was established in male SD rats by 2 weeks of CUMS combined with LPS. The models were verified by behavioral tests, namely SPT, OFT, EPM, and qRT‐PCR for pro‐inflammatory cytokines. Such depressed rats were administered human umbilical cord MSCs (hUC‐MSCs) via the tail vein once a week for 2 and 4 weeks. The homing capacity was confirmed by detection of the fluorescent dye on day 7 after the hUC‐MSCs were labeled with CM‐Dil and administered. The expression of GFAP in astrocytes serves as a biomarker of CNS disorders and IBA1 in microglia serves as a marker of microglia activation were detected by immunohistochemistry at 2 and 4 weeks after final administration of hUC‐MSCs. At the same time, transcriptomics of rat hippocampal tissue, proteomic and metabolomic analysis of the serum from the normal, depressed, and treated rats were also compared.ResultsReliable models of rat depression were successfully induced by treatments of CUMS combined with LPS. Rat depression behaviors, pro‐inflammatory cytokines, and morphological disorders of the hippocampus associated with depression were reversed in 4 weeks by hUC‐MSC treatment. hUC‐MSCs could reach the hippocampus CA1 region through the blood circulation on day 7 after administration owing to the disruption of blood brain barrier (BBB) by microglial activation from depression. Differentiations of whole‐genome expression, protein, and metabolite profiles between the normal and depression‐modeled rats, which were analyzed by transcriptomic, proteomics, and metabolomics, further verified the high association with depression behaviors.ConclusionsRat depression can be reversed or recovered by treatment with hUC‐MSCs.

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Section: Discussionmentioning

confidence: 99%

Human umbilical cord mesenchymal stem cells reverse depression in rats induced by chronic unpredictable mild stress combined with lipopolysaccharide

Wang,

Li,

Song

et al. 2024

CNS Neurosci Ther

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“…Social Defeat induces molecular as well as physiological changes in the brain. Multiple studies have been done to see the effect of chronic stress like social defeat in different brain regions like hippocampus, amygdala, pre-frontal cortex etc (Colyn et al , 2019; Fan et al , 2021; Iñiguez et al , 2014, 2016). In this present study, we analysed protein profile of hypothalamus, the major constituent of the HPA axis to understand the molecular changes that take place in hypothalamus on subjection to social defeat stress and whether we can correlate them to the response to stress.…”

Section: Discussionmentioning

confidence: 99%

Hypothalamic Protein Profiling from Mice Subjected to Social Defeat Stress

Mitra

Kumar

Samanta

et al. 2023

Preprint

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The Hypothalmic-pituitary axis also known as the HPA axis is central to stress response. It also acts as the relay centre between the body and the brain. We analysed hypothalamic proteome from mice subjected to chronic social defeat paradigm using iTRAQ based quantitative proteomics in identify changes associated with stress response. We identified greater than 2000 proteins processing our samples analysed through Q-Exactive (Thermo) and Orbitrap Velos (Thermo) at 5% FDR. Analysis of data procured from the runs showed that the proteins whose levels were affected belonged primarily to mitochondrial and metabolic processes, translation, complement pathway among others. We also found increased levels of fibrinogen, myelin basic protein (MBP) and neurofilaments (NEFL, NEFM, NEFH) in the hypothalamus from socially defeated mice. Interestingly these proteins are found upregulated in blood and CSF of subjects exposed to trauma and stress. Since hypothalamus is in direct contact of blood and CSF, their utility as biomarkers in depression holds an impressive probability and should be validated in clinical samples.

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“…Given the profound role of the brain as the central organ for stress sensing and response as well as the regulation of systemic stress, the goal of this study was to define the major molecular changes of stress-associated genes and metabolites in an unbiased manner. Previous rodent studies have been predominantly conducted under repeated or chronic stress conditions [ 27 , 28 , 32 , 36 , 39 , 42 , 43 , 47 ]. However, compared to our understanding of the effects of chronic stress, the impacts of acute stress (AS) on the brain remain largely unexplored.…”

Section: Discussionmentioning

confidence: 99%

“…Other omics-based approaches (e.g., proteomics, metabolomics) have often been adopted to explore stress-linked molecular alterations in the brain. Various stress paradigms such as chronic social defeat stress, prenatal stress, and restraint have been used to identify molecular changes in different brain regions, classically associated with anxiety and depression-related behaviors including the prefrontal cortex, hippocampus, amygdala, and nucleus accumbens [ 33 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ]. However, our knowledge on the biochemical and molecular changes occurring in the brain in response to acute stress remains largely insufficient.…”

Section: Introductionmentioning

confidence: 99%

Metabolic and Transcriptomic Signatures of the Acute Psychological Stress Response in the Mouse Brain

2023

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Acute stress response triggers various physiological responses such as energy mobilization to meet metabolic demands. However, the underlying molecular changes in the brain remain largely obscure. Here, we used a brief water avoidance stress (WAS) to elicit an acute stress response in mice. By employing RNA-sequencing and metabolomics profiling, we investigated the acute stress-induced molecular changes in the mouse whole brain. The aberrant expression of 60 genes was detected in the brain tissues of WAS-exposed mice. Functional analyses showed that the aberrantly expressed genes were enriched in various processes such as superoxide metabolism. In our global metabolomic profiling, a total of 43 brain metabolites were significantly altered by acute WAS. Metabolic pathways upregulated from WAS-exposed brain tissues relative to control samples included lipolysis, eicosanoid biosynthesis, and endocannabinoid synthesis. Acute WAS also elevated the levels of branched-chain amino acids, 5-aminovalerates, 4-hydroxy-nonenal-glutathione as well as mannose, suggesting complex metabolic changes in the brain. The observed molecular events in the present study provide a valuable resource that can help us better understand how acute psychological stress impacts neural functions.

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Proteomic and metabolomic characterization of amygdala in chronic social defeat stress rats

Cited by 12 publications

References 71 publications

Human umbilical cord mesenchymal stem cells reverse depression in rats induced by chronic unpredictable mild stress combined with lipopolysaccharide

Human umbilical cord mesenchymal stem cells reverse depression in rats induced by chronic unpredictable mild stress combined with lipopolysaccharide

Hypothalamic Protein Profiling from Mice Subjected to Social Defeat Stress

Metabolic and Transcriptomic Signatures of the Acute Psychological Stress Response in the Mouse Brain

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