The Potential Role of Very Small Embryonic-Like Stem Cells in the Neuroinflammation Induced by Social Isolation Stress: Introduction of a New Paradigm

Abstract

Background: 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. Methods: 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. Results: 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. 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.

Role of hypothalamic-pituitary adrenal-axis, toll-like receptors, and macrophage polarization in pre-atherosclerotic changes induced by social isolation stress in mice

“…Based on our previous study, after sacrificing mice, we resected femur and tibia from surrounding tissue of both normal and socially isolated animals, and then flush the bones with warm medium (5% fetal bovine serum (FBS), + 1% Streptomycin) through a 70 µm nylon 31 . Then centrifuged the samples 250×g for 10 min in 4 °C; and discarded the supernatant and resuspend the cells with approximately 25 ml of medium 32 . We checked and counted the cells in a counting chamber with a light microscope and calculated the number of observed cells.…”

High risk of drug toxicity in social isolation stress due to liver dysfunction: Role of oxidative stress and inflammation

“…temperature: 22 ± 2°C, humidity: 50 ± 10%, 12‐h light‐dark cycle, and ad‐libitum access to food and water for a period of 5 weeks. Socially conditioned mice were placed in Plexiglas boxes (25 cm × 25 cm × 15 cm) (6 mice per cage) and IC animals were placed individually in Plexiglas boxes (24 cm × 17 cm × 12 cm) (Haj‐Mirzaian et al., 2017, Haj‐Mirzaian et al., 2020). In order to diminish handling and social interaction cages of IC animals were cleaned weekly by the same experimenter.…”

“…We also measured serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6), TNFα, and the gene expression of CYP450 in order to detect the extent of inflammation and the hepatic enzymatic capacity, respectively. -Mirzaian et al, 2017, Haj-Mirzaian et al, 2020. In order to diminish handling and social interaction cages of IC animals were cleaned weekly by the same experimenter.…”