Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

A Short Oro-Gastric Imipramine Administration in Brucella abortus 2308 Infected Mice Decreases CFU Count at the Spleen; Improves the IFN-γ/IL-6 Ratio; Restores Serotonin Levels in the Hippocampus, Muscular Strength, and Mood

Version 1 : Received: 5 March 2022 / Approved: 8 March 2022 / Online: 8 March 2022 (11:04:46 CET)

How to cite: Maldonado-Tapia, J.O.; Maldoando-García, J.L.; Pérez-Sánchez, G.; Becerril-Villanueva, E.; Alvarez-Herrera, S.; Pavón, L.; Gutiérrez-Ospina, G.; López-Santiago, R.; Moreno-Lafont, M.C. A Short Oro-Gastric Imipramine Administration in Brucella abortus 2308 Infected Mice Decreases CFU Count at the Spleen; Improves the IFN-γ/IL-6 Ratio; Restores Serotonin Levels in the Hippocampus, Muscular Strength, and Mood. Preprints 2022, 2022030123 (doi: 10.20944/preprints202203.0123.v1). Maldonado-Tapia, J.O.; Maldoando-García, J.L.; Pérez-Sánchez, G.; Becerril-Villanueva, E.; Alvarez-Herrera, S.; Pavón, L.; Gutiérrez-Ospina, G.; López-Santiago, R.; Moreno-Lafont, M.C. A Short Oro-Gastric Imipramine Administration in Brucella abortus 2308 Infected Mice Decreases CFU Count at the Spleen; Improves the IFN-γ/IL-6 Ratio; Restores Serotonin Levels in the Hippocampus, Muscular Strength, and Mood. Preprints 2022, 2022030123 (doi: 10.20944/preprints202203.0123.v1).

Abstract

Brucellosis infection induces fever, chills, sweats, headache, myalgia, arthralgia, anorexia, fa-tigue, and mood disorders. In mice, it causes a rise in IL-6, TNF-, and IFN-; and reduces sero-tonin and dopamine levels in hippocampus. There is loss in muscle strength and equilibrium and increased anxiety and hopelessness. Imipramine (ImiP) is a tricyclic antidepressant that increases the capacity of macrophages to destroy intracellular microorganisms in vivo. The effect of ImiP was evaluated in Balb/c mice infected with Brucella abortus 2308. Serum levels were determined in IFN-, IL-6, TNF-, IL-12, MCP-1, and IL-10 by FACS; the bacterial count in the spleen, by CFU; the serotonin concentration in the hippocampus, by HPLC; and strength, equilibrium, and mood by behavioral tests. Our results showed that infected vs. control mice had a significant rise in lev-els of IFN-, IL-6, TNF-, and IL-12 with a low IFN-/IL-6 ratio, elevated bacterial-counts, alter-ations in serotonin concentration at hippocampus, and decreased muscular strength, equilibrium, and mood. Infected mice treated with ImiP vs. infected mice showed: 1) improved mood; 2) in-creased hippocampal serotonin availability, splenic dendritic cells, and macrophage phagocytic activity; and 3) upturn inflammation and reduced CFU ability. Our results support that ImiP fa-vors positive outcomes in subjects handling Brucella infections likely by improving psychoim-mune resilience.

Keywords

Depression; psychoimmune resilience; tricyclic antidepressants; serotonin; modulation of inflammatory response; infectious diseases

Subject

LIFE SCIENCES, Immunology

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