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Human type 2 macrophages biologically active soluble products in the editing of stress-induced depressive-like behavior

Published online by Cambridge University Press:  13 August 2021

E. Markova*
Affiliation:
Neuroimmunology Lab, State Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation
E. Shevela
Affiliation:
Cellular Immunotherapy Laboratory, State Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation
M. Knyazheva
Affiliation:
Neuroimmunology Lab, State Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation
I. Savkin
Affiliation:
Neuroimmunology Lab, State Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation
T. Amstislavskaya
Affiliation:
Translational Biopsychiatry Lab, Research Institute of Neurosciences and Medicine, Novosibirsk, Russian Federation
A. Ostanin
Affiliation:
Cellular Immunotherapy Laboratory, State Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation
E. Chernykh
Affiliation:
Cellular Immunotherapy Laboratory, State Research Institute of Fundamental and Clinical Immunology, Novosibirsk, Russian Federation
*
*Corresponding author.

Abstract

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Introduction

In the scientific world widely discussed phenomenon of “cytokine-induced depression”. Macrophages have high plasticity and are able to control the inflammatory response; in particular, anti-inflammatory type-2 macrophages have a pronounced potential due to complex soluble factors production.

Objectives

We have developed an original method for the type-2 macrophages generation; the resulting macrophages are characterized by the high level of a whole range of neurotrophic, neuroprotective, proangiogenic and anti-inflammatory factors production. The aim of the study was to investigate effects of human type-2 macrophages soluble products on behavioral phenotype and brain cytokines synthesis in depressive-like animals.

Methods

Type-2 macrophages were generated by culturing an adherent fraction of mononuclear cells with 50 ng/ml recombinant human GM-CSF in serum deprivation conditions for 7 days. (CBA x C57Bl/6)F1 depressive-like male mice, developed under the long-term social stress, were undergoing the human type-2 macrophages conditioned medium intranasal administration (60 ml twice daily for one animal) for 6 days. Mice behavioral phenotyping was carried out using an automatic registration system (Noldus Information Technology). Cytokines were determined by ELISA.

Results

Depressive-like mice behavioral phenotyping after type-2 macrophages conditioned medium administration revealed anhedonia decrease, motor activity stimulation in the open field and forced swimming tests, anxiety reduction in elevated plus maze. Behavioral changes were recorded against the pro-inflammatory cytokines (TNF-α, IL-1β, IL- 6, INFγ) decrease in striatum and hippocampus, as well as anti-inflammatory IL- 10 increase in hippocampus and hypothalamus.

Conclusions

Results demonstrated the effectiveness of human type-2 macrophages biologically active soluble products in relation to the stress-induced depressive-like behavior editing

Disclosure

No significant relationships.

Type
Abstract
Creative Commons
Creative Common License - CCCreative Common License - BY
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited.
Copyright
© The Author(s), 2021. Published by Cambridge University Press on behalf of the European Psychiatric Association
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