scholarly journals Analysis of Chronic Mild Stress-Induced Hypothalamic Proteome: Identification of Protein Dysregulations Associated With Vulnerability and Resiliency to Depression or Anxiety

2021 ◽  
Vol 14 ◽  
Author(s):  
Weibo Gong ◽  
Wei Liao ◽  
Chui Fang ◽  
Yanchen Liu ◽  
Hong Xie ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Chronic Mild Stress ◽  
Regulation System ◽  
Mild Stress ◽  
Absolute Quantitation ◽  
Protein Targets ◽  
Proteomic Approach ◽  
Parallel Reaction Monitoring ◽  
Independent Analysis ◽  
Isobaric Tags

Chronic stress as a known risk factor leads to hyperactivity of the hypothalamus-pituitary-adrenal (HPA) axis in both depression and anxiety. However, the stress-induced dysfunction of the HPA axis in these disorders especially the common and unique molecular dysregulations have not been well-explored. Previously, we utilized a chronic mild stress (CMS) paradigm to segregate and gain depression-susceptible, anxiety-susceptible, and insusceptible groups. In this study, we continue to examine the possible protein expression alterations of the hypothalamus as the center of the HPA axis in these three groups by using a proteomic approach. Though isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative analysis, a total of 593 dysregulated proteins were identified. These were potentially associated with vulnerability and adaptability of CMS-caused depression or anxiety and therefore might become novel investigative protein targets. Further independent analysis using parallel reaction monitoring (PRM) indicated that 5, 7, and 21 dysregulated proteins were specifically associated with depression-susceptible, anxiety-susceptible, and insusceptible groups, respectively, suggesting that the same CMS differently affected the regulation system of the rat hypothalamic proteome. In summary, the current proteomic research on the hypothalamus provided insights into the specific and common molecular basis for the HPA dysfunction mechanisms that underlie resiliency and vulnerability to stress-induced depression or anxiety.

scholarly journals Proteomic Insights Into Susceptibility and Resistance to Chronic-Stress-Induced Depression or Anxiety in the Rat Striatum

2021 ◽  
Vol 8 ◽  
Author(s):  
Xiao Cai ◽  
Chen Yang ◽  
Jin Chen ◽  
Weibo Gong ◽  
Faping Yi ◽  
...  
Keyword(s):  
Chronic Stress ◽  
Chronic Mild Stress ◽  
Rat Striatum ◽  
Mild Stress ◽  
Absolute Quantitation ◽  
Protein Targets ◽  
Parallel Reaction Monitoring ◽  
Key Factor ◽  
Depression Disorders ◽  
Isobaric Tags

Chronic stress is a key factor for the onset of anxiety and depression disorders. However, the stress-induced common and unique molecular basis of the two psychiatric disorders is not fully known and still needs to be explored. Previously, we employed a chronic mild stress (CMS) procedure to induce a rat model including depression-susceptible (Dep-Sus), anxiety-susceptible (Anx-Sus), and insusceptible (Insus) cohorts. In this work, we continuously analyze the striatal proteomes of the three stressed cohorts by the use of comparative proteomics and bioinformatics approaches. Through isobaric tags for relative and absolute quantitation (iTRAQ)-based analysis, 386 abnormally expressed proteins in total were identified. These deregulated proteins are involved in various biological functions and significant pathways that are potentially connected with resistance and susceptibility to CMS-caused anxious- or depressive-like behaviors and, hence, could act as suggestive protein targets. A further parallel reaction monitoring-based independent investigation shows that alterations in Pak5, Dgkg, Scn4b, Rb1cc1, and Acin1; Ggps1, Fntb, Nudt19, Ufd1, and Ndufab1; and Dnajb12, Hbb2, Ap2s1, Ip6k1, and Stk4 were specifically connected with Dep-Sus, Anx-Sus, or Insus groups, respectively, potentially indicating that identical CMS treatment results in the different changes in the striatal protein regulations. Overall, our current proteomics study of the striatum provides an important molecular foundation and comprehensive insights into common and specific deregulations correlated with pathophysiological mechanisms that underlie resistance and susceptibility to chronic stress–induced anxiety or depression.

scholarly journals Chronic mild stress-induced protein dysregulations correlated with susceptibility and resiliency to depression or anxiety revealed by quantitative proteomics of the rat prefrontal cortex

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wei Liao ◽  
Yanchen Liu ◽  
Lixiang Wang ◽  
Xiao Cai ◽  
Hong Xie ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Significant Risk ◽  
Chronic Mild Stress ◽  
Significant Risk Factor ◽  
Regulation System ◽  
Mild Stress ◽  
Absolute Quantitation ◽  
Prefrontal Cortical ◽  
Independent Analysis ◽  
Isobaric Tags

AbstractChronic stress is a significant risk factor for depression as well as anxiety disorders. Yet, the stress-induced specific and common molecular dysregulations of these disorders have not been fully understood. Previously, we constructed a chronic mild stress (CMS) rat model to separate and obtain depression-susceptible, anxiety-susceptible, and insusceptible groups. In this study, the prefrontal cortical proteomes of the three stressed groups were comparatively profiled utilizing isobaric tags for relative and absolute quantitation (iTRAQ)-coupled tandem mass spectrometry approach. A total of 212 protein dysregulations were identified, potentially correlating to susceptibility or resilience to CMS-induced depression or anxiety, and thus might serve as potential protein targets for further investigation. In addition, independent analysis by parallel reaction monitoring identified changes in Gfap, Rhog, Gnai2, Ppp1r1b, and Uqcrh; Tubb6, Urod, Cul1, Spred1, and Gpcpd1; Acadl, Ppp1r1a, Grm2, Mtor, Lsm8, Cplx2, and Tsta3 that were distinctly correlated to depression-susceptible, anxiety-susceptible, or insusceptible groups, respectively. This suggested that identical CMS had different effects on the protein regulation system of the rat prefrontal cortex. Collectively, the present proteomics study of the prefrontal cortex established a significant molecular basis and offered new insights into the specificity and commonality of pathophysiologic mechanisms underlying susceptibility and resiliency to stress-induced depression or anxiety.

scholarly journals Proteomic Response of Rat Pituitary Under Chronic Mild Stress Reveals Insights Into Vulnerability and Resistance to Anxiety or Depression

2021 ◽  
Vol 12 ◽  
Author(s):  
Fenfang Tian ◽  
Dan Liu ◽  
Jin Chen ◽  
Wei Liao ◽  
Weibo Gong ◽  
...  
Keyword(s):  
Hpa Axis ◽  
Significant Risk ◽  
Regulatory System ◽  
Proteome Analysis ◽  
Chronic Mild Stress ◽  
Significant Risk Factor ◽  
Mild Stress ◽  
Protein Targets ◽  
Independent Analysis ◽  
Rat Pituitary

Chronic stress as one of the most significant risk factor can trigger overactivity of hypothalamic-pituitary-adrenal (HPA) axis in depression as well as anxiety. Yet, the shared and unique neurobiological underpinnings underlying the pituitary abnormality in these two disorders have not been made clear. We previously have established depression-susceptible, anxiety-susceptible and insusceptible groups using a valid chronic mild stress (CMS) model. In this work, the possible protein expression changes in the rat pituitary of these three groups were continuously investigated through the use of the comparative quantitative proteomics and bioinformatics approaches. The pituitary-proteome analysis identified totally 197 differential proteins as a CMS response. These deregulated proteins were involved in diverse biological functions and significant pathways potentially connected with the three different behavioral phenotypes, likely serving as new investigative protein targets. Afterwards, parallel reaction monitoring-based independent analysis found out that expression alterations in Oxct1, Sec24c, Ppp1cb, Dock1, and Coq3; Lama1, Glb1, Gapdh, Sccpdh, and Renbp; Sephs1, Nup188, Spp1, Prodh1, and Srm were specifically linked to depression-susceptible, anxiety-susceptible and insusceptible groups, respectively, suggesting that the same CMS had different impacts on the pituitary protein regulatory system. Collectively, the current proteomics research elucidated an important molecular basis and furnished new valuable insights into neurochemical commonalities and specificities of the pituitary dysfunctional mechanisms in HPA axis underlying vulnerability and resistance to stress-induced anxiety or depression.

scholarly journals Hippocampal proteomic changes of susceptibility and resilience to depression or anxiety in a rat model of chronic mild stress

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Min Tang ◽  
Haojun Huang ◽  
Shuiming Li ◽  
Mi Zhou ◽  
Zhao Liu ◽  
...  
Keyword(s):  
Rat Model ◽  
Molecular Mechanisms ◽  
Chronic Mild Stress ◽  
Immunoblot Analysis ◽  
Regulation Mechanism ◽  
Mild Stress ◽  
Depression And Anxiety ◽  
Absolute Quantitation ◽  
Protein Targets ◽  
Isobaric Tags

Abstract Chronic stressful occurrences are documented as a vital cause of both depression and anxiety disorders. However, the stress-induced molecular mechanisms underlying the common and distinct pathophysiology of these disorders remains largely unclear. We utilized a chronic mild stress (CMS) rat model to differentiate and subgroup depression-susceptible, anxiety-susceptible, and insusceptible rats. The hippocampus was analyzed for differential proteomes by combining mass spectrometry and the isobaric tags for relative and absolute quantitation (iTRAQ) labeling technique. Out of 2593 quantified proteins, 367 were aberrantly expressed. These hippocampal protein candidates might be associated with susceptibility to stress-induced depression or anxiety and stress resilience. They provide the potential protein systems involved in various metabolic pathways as novel investigative protein targets. Further, independent immunoblot analysis identified changes in Por, Idh2 and Esd; Glo1, G6pdx, Aldh2, and Dld; Dlat, Ogdhl, Anxal, Tpp2, and Sdha that were specifically associated to depression-susceptible, anxiety-susceptible, or insusceptible groups respectively, suggesting that identical CMS differently impacted the mitochondrial and metabolic processes in the hippocampus. Collectively, the observed alterations to protein abundance profiles of the hippocampus provided significant and novel insights into the stress regulation mechanism in a CMS rat model. This might serve as the molecular basis for further studies that would contributed to a better understanding of the similarities and differences in pathophysiologic mechanisms underlying stress-induced depression or anxiety, and stress resiliency.

Comparative Proteomics of Rat Olfactory Bulb Reveal Insights Into Susceptibility and Resilience to Chronic-Stress-Induced Depression or Anxiety

2021 ◽  
Author(s):  
Dan Liu ◽  
Xiao Cai ◽  
Lixiang Wang ◽  
Faping Yi ◽  
Wei Liao ◽  
...  
Keyword(s):  
Olfactory Bulb ◽  
Chronic Stress ◽  
Proteome Analysis ◽  
Chronic Mild Stress ◽  
Maladaptive Behavior ◽  
Regulation System ◽  
Mild Stress ◽  
Potential Candidate ◽  
Bioinformatics Analyses ◽  
Protein Targets

Abstract As a main risk factor of both anxiety and depression, chronic stress can cause the abnormality of olfactory bulb (OB). However, the unique and common neurobiological underpinnings underlying the OB dysfunction of these two disorders are still poorly understood. Previously, we have built depression-susceptible (Dep-Sus), anxiety-susceptible (Anx-Sus) and insusceptible (Insus) groups through the use of a valid chronic mild stress (CMS) regime. To continuously explore the protein expression changes in these three groups, comparative quantitative proteomics analysis was conducted on the rat OB as crucial part of the olfactory system. Next, bioinformatics analyses were implemented whereas protein expressions were independently analyzed by parallel reaction monitoring (PRM) or Western blot (WB). The OB-proteome analysis identified totally 133 differentially expressed proteins as a CMS response. These deregulated proteins were involved in multiple functions and significant pathways potentially correlated with phenotypes of maladaptive behavior of depression or anxiety as well as adaptive behavior, and hence might act as potential candidate protein targets. The subsequent PRM-based or WB-based analyses showed that changes in Nefl, Mtmr7 and Tk2; Prkaca, Coa3, Cox6c2, Lamc1 and Tubal3; and Pabpn1, Nme3, Sos1 and Lum were uniquely associated with Dep-Sus, Anx-Sus, and Insus groups, respectively. This suggested that the identical CMS differently impacted the olfactory protein regulation system. To sum up, our present data as a useful proteomics underpinning provided the common and distinct molecular insights into the biochemical understanding of OB dysfunction underlying susceptibility and resiliency to chronic-stress-induced anxiety or depression.

scholarly journals Partial Proteome Map of Campylobacter Jejuni Strain Nctc11168 by Gel-Free Proteomics Analysis

2014 ◽  
Vol 2 (4) ◽  
pp. 464-477
Author(s):  
Zilun Shi ◽  
Chris Dawson ◽  
Stephen L.W. On ◽  
Malik Altaf Hussain
Keyword(s):  
Campylobacter Jejuni ◽  
Foodborne Pathogen ◽  
Brain Heart Infusion ◽  
Cell Protein ◽  
Absolute Quantitation ◽  
Whole Cell ◽  
Itraq Analysis ◽  
Proteomic Approach ◽  
Whole Cell Protein ◽  
Isobaric Tags

A proteome map of the foodborne pathogen Campylobacter jejuni NCTC11168 was analyzed using a state-of-the-art gel-free proteomic approach for the first time. A whole cell protein extract was prepared from the C. jejuni strain NCTC11168 grown in brain heart infusion (BHI) broth at 42°C under microaerobic conditions. A gel-free technique using isobaric tags for relative and absolute quantitation (iTRAQ) was employed to create a protein expression profile of the strain. Liquid chromatography-mass spectrometry (LC-MS/MS) was used to identify the proteins. Protein functionalities were searched to classify them. A total of 235 proteins were identified in the whole cell protein fraction of C. jejuni NCTC11168 cells using iTRAQ analysis. Functional grouping of the identified proteins showed that forty percent of these proteins were associated with energy metabolism, protein synthesis and genetic information processing. iTRAQ was faster, easier and proved more sensitive than two-dimensional gel-based proteomics approaches previously applied to C. jejuni, making it an attractive tool for further studies of cellular physiological response. DOI: http://dx.doi.org/10.3126/ijasbt.v2i4.11253  Int J Appl Sci Biotechnol, Vol. 2(4): 464-477 

scholarly journals N-3 Polyunsaturated Fatty Acid Improved Depression via Neuroendocrine and Serotonergic System in Post-Menopausal Rats with Maternal Separation and Chronic Mild Stress

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1199-1199
Author(s):  
Jeong-Eun Choi ◽  
Yongsoon Park
Keyword(s):  
Hpa Axis ◽  
Maternal Separation ◽  
Chronic Mild Stress ◽  
Female Rats ◽  
Serotonin Level ◽  
Mild Stress ◽  
Total N ◽  
Serotonergic Pathway ◽  
Post Menopausal ◽  
Hpa Axis Activity

Abstract Objectives The purpose of the present study was to investigate the hypothesis that lifetime n-3 polyunsaturated fatty acids (PUFA) intake improved depression through serotonergic pathway in post-menopausal rats with chronic mild stress (CMS) and maternal separation (MS). Methods Female rats were fed diets with 0% or 1 energy % n-3 PUFA during lifetime from embryonic day (ED) 0 to postnatal day (PND) 112, or 1% n-3 PUFA before weaning (ED 0-PND 20), or after weaning (PND 20–112). The rats in four diet group were allocated to brief separation from dam (non-MS group) or long-term separation (MS group) on PND 2–14, and then underwent CMS on PND 91–105 after ovariectomy. Thus, there were eight groups in total (n = 8/group). Results MS + CMS increased depressive behaviors, and modified hypothalamic-pituitary-adrenal (HPA) axis activity, inflammation, serotonergic and glutamatergic neurotransmission, and related miRNAs as compared to CMS alone. N-3 PUFA decreased depressive behaviors by decreasing immobility while increasing swimming during forced swim test, and increasing sucrose preference in rats with MS + CMS and with CMS. N-3 PUFA decreased HPA axis activity by modifying expressions of corticotrophin releasing factor and glucocorticoid receptor, and levels of adrenocorticotropic hormone and corticosterone. N-3 PUFA also reduced levels of TNF-α, IL-1β, IL-6, PGE2, and miRNA-218, and increased serotonergic neurotransmission, including expressions of cAMP response element binding protein, brain-derived neurotrophic factor and serotonin 1A receptor, and serotonin level, and expression of miRNA-155. In addition, lifetime supplementation of n-3 PUFA had greater effect than pre- or post-supplementation. N-3 PUFA had no effect on glutamatergic pathway including α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor and N-methyl-D-aspartate receptor. Conclusions The present study suggested that lifetime n-3 PUFA improved depression in post-menopausal rats with MS + CMS through modulation of serotonergic pathway by decreasing HPA axis activity but not glutamatergic pathway. Funding Sources This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (NRF-2018R1A2B6002486).

Plasma-based proteomics reveals lipid metabolic and immunoregulatory dysregulation in post-stroke depression

2014 ◽  
Vol 29 (5) ◽  
pp. 307-315 ◽  
Author(s):  
Y. Zhan ◽  
Y.-T. Yang ◽  
H.-M. You ◽  
D. Cao ◽  
C.-Y. Liu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Expression Profiles ◽  
Absolute Quantitation ◽  
Post Stroke ◽  
Reactive Protein ◽  
Proteomic Approach ◽  
Psychiatric Complication ◽  
Post Stroke Depression ◽  
Healthy Control ◽  
Isobaric Tags

AbstractBackground:Post-stroke depression (PSD) is the most common psychiatric complication facing stroke survivors and has been associated with increased distress, physical disability, poor rehabilitation, and suicidal ideation. However, the pathophysiological mechanisms underlying PSD remain unknown, and no objective laboratory-based test is available to aid PSD diagnosis or monitor progression.Methods:Here, an isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach was performed to identify differentially expressed proteins in plasma samples obtained from PSD, stroke, and healthy control subjects.Results:The significantly differentiated proteins were primarily involved in lipid metabolism and immunoregulation. Six proteins associated with these processes – apolipoprotein A-IV (ApoA-IV), apolipoprotein C-II (ApoC-II), C-reactive protein (CRP), gelsolin, haptoglobin, and leucine-rich alpha-2-glycoprotein (LRG) – were selected for Western blotting validation. ApoA-IV expression was significantly upregulated in PSD as compared to stroke subjects. ApoC-II, LRG, and CRP expression were significantly downregulated in both PSD and HC subjects relative to stroke subjects. Gelsolin and haptoglobin expression were significantly dysregulated across all three groups with the following expression profiles: gelsolin, healthy control > PSD > stroke subjects; haptoglobin, stroke > PSD > healthy control.Conclusions:Early perturbation of lipid metabolism and immunoregulation may be involved in the pathophysiology of PSD. The combination of increased gelsolin levels accompanied by decreased haptoglobin levels shows promise as a plasma-based diagnostic biomarker panel for detecting increased PSD risk in post-stroke patients.

scholarly journals Identification of Novel Escherichia coli Ribosome-Associated Proteins Using Isobaric Tags and Multidimensional Protein Identification Techniques

2007 ◽  
Vol 189 (9) ◽  
pp. 3434-3444 ◽  
Author(s):  
M. Jiang ◽  
S. M. Sullivan ◽  
A. K. Walker ◽  
J. R. Strahler ◽  
P. C. Andrews ◽  
...  
Keyword(s):  
Ribosomal Proteins ◽  
Protein Identification ◽  
Ribosomal Subunit ◽  
Ribosome Assembly ◽  
Absolute Quantitation ◽  
Proteomic Approach ◽  
Assembly Factors ◽  
Associated Proteins ◽  
Isobaric Tags

ABSTRACT Biogenesis of the large ribosomal subunit requires the coordinate assembly of two rRNAs and 33 ribosomal proteins. In vivo, additional ribosome assembly factors, such as helicases, GTPases, pseudouridine synthetases, and methyltransferases, are also critical for ribosome assembly. To identify novel ribosome-associated proteins, we used a proteomic approach (isotope tagging for relative and absolute quantitation) that allows for semiquantitation of proteins from complex protein mixtures. Ribosomal subunits were separated by sucrose density centrifugation, and the relevant fractions were pooled and analyzed. The utility and reproducibility of the technique were validated via a double duplex labeling method. Next, we examined proteins from 30S, 50S, and translating ribosomes isolated at both 16°C and 37°C. We show that the use of isobaric tags to quantify proteins from these particles is an excellent predictor of the particles with which the proteins associate. Moreover, in addition to bona fide ribosomal proteins, additional proteins that comigrated with different ribosomal particles were detected, including both known ribosomal assembly factors and unknown proteins. The ribosome association of several of these proteins, as well as others predicted to be associated with ribosomes, was verified by immunoblotting. Curiously, deletion mutants for the majority of these ribosome-associated proteins had little effect on cell growth or on the polyribosome profiles.

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