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

Fenfang Tian,Dan Liu,Faping Yi,Wei Liao,Jian Zhou,Liang Xie,Jin Chen,Weibo Gong,Rongzhong Huang

doi:10.3389/fgene.2021.751999

Abstract

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.

Highlights

Anxiety and depression are two severe and chronic neuropsychiatric illnesses
We utilized the EPM test for indexing the anxious-like symptom. Based on these testing data, a subset of the Dep-Sus, Anx-Sus, Insus, and Ctrl groups was obtained. These results indicated that we could effectively utilized the chronic mild stress (CMS) model to investigate the neurobiological processes associated with the resistance and vulnerability of stressrelated anxious or depressive disorders
We investigated the effects of CMS on the expression of the rat pituitary proteins through the use of isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomics analyses (Figure 1A)

Summary

Introduction

Anxiety and depression are two severe and chronic neuropsychiatric illnesses. The prevalences of these disorders are increasing, potentially representing a significant clinical challenge. Pituitary Proteomic Response to CMS stress can result in the adverse health impacts when it increases beyond a certain level, thereby causing anxiety and depression (Chang and Grace, 2014; Tian et al, 2020). To model the adverse environment factors that affect humans, chronic mild stress (CMS) protocol has been commonly employed to induce anxious-like and depressive-like behaviors in rodent animals (Chang and Grace, 2014; Zhou et al, 2016). To identify the potential biological relationships between CMS and pathological changes, it may be useful to focus on the neurobiological components and processes reflecting adaptive and maladaptive responses to the stress-caused anxiety and depression

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Conclusion