The potential role of very small embryonic-like stem cells in the neuroinflammation induced by social isolation stress: Introduction of a new paradigm

Arvin Haj-Mirzaian,Ayda Khosravi,Arya Haj-Mirzaian,Alireza Rahbar,Kiana Ramezanzadeh,Rajan Nikbakhsh,Fardad Pirri,Bhenam Talari,Maria Ghesmati,Rambod Nikbakhsh,Ahmad Reza Dehpour

doi:10.1016/j.brainresbull.2020.07.006

Abstract

Lack of social contacts could induce psychiatric features and lead to various behavioral and neurochemical abnormalities in rodents. Social isolation stress (SIS) is a valid paradigm of depressive- and anxiety-like behaviors in animals. It has demonstrated that psychiatric disorder could affect the peripheral blood population of very small embryonic-like stem cells (VSELs). The aim of the current study is to evaluate the role of VSELs in behavioral impairments induced by SIS through neuroinflammation in mice. Behavioral experiments were evaluated by using forced swimming test (FST), open field test (OFT), and splash test in male NMRI mice. In addition, plasma and bone marrow samples, as well as hippocampus, were collected to evaluate the population of VSELs, nitrite level, and inflammatory cytokines by using flow cytometry and ELISA. Behavioral tasks showed that SIS could induce depressive- and anxiety-like behaviors in mice. Data obtained from flow cytometry showed that VSELs significantly increased in socially isolated animals in bone marrow, peripheral blood, and hippocampus. Also, TNF-α, IL-1β, and IL-6 significantly increased in hippocampal and plasma samples in socially isolated animals. Correlation analysis indicated that mice with higher VSELs counts have better results in behavioral tasks, and lower pro-inflammatory cytokines as well as nitrite level in mice. In conclusion, VSELs could be used as a biological marker to enhance diagnostic accuracy as well as predicting the prognosis. Also, increment in the VSELs counts might decrease the neuro-inflammation and subsequently improve the behavioral impairments induced by SIS.

Highlights

It has been well documented that lack of social contacts could induce psychiatric features and lead to various behavioral and neurochemical abnormalities in rodents [1]
very small embryonic-like stem cells (VSELs) could be used as a biological marker to enhance diagnostic accuracy as well as predicting the prognosis
At the first part of this study, we evaluated the effect of Social isolation stress (SIS) on some behavioral tasks including Forced swimming test (FST), splash test, and Open-field test (OFT), and Hole-board test (HBT)

Summary

Introduction

It has been well documented that lack of social contacts could induce psychiatric features and lead to various behavioral and neurochemical abnormalities in rodents [1]. The social isolation stress (SIS), as a chronic stressor, is a valid paradigm, which has been used as an animal model to study neurobehavioral changes [2, 3]. Recent studies have demonstrated that the population of stem cells in the peripheral blood could be affected in an individual diagnosed with a psychiatric disorder. Lack of social contacts could induce psychiatric features and lead to various behavioral and neurochemical abnormalities in rodents. Social isolation stress (SIS) is a valid paradigm of depressiveand anxiety-like behaviors in animals. It has demonstrated that psychiatric disorder could affect the peripheral blood population of very small embryonic-like stem cells (VSELs). The aim of the current study is to evaluate the role of VSELs in behavioral impairments induced by SIS through neuroinflammation in mice

Objectives

Methods

Results

Discussion

Conclusion