Pharmaceuticals (Oct 2023)

Imipramine Administration in <i>Brucella abortus 2308</i>-Infected Mice Restores Hippocampal Serotonin Levels, Muscle Strength, and Mood, and Decreases Spleen CFU Count

  • José Luis Maldonado-García,
  • Gilberto Pérez-Sánchez,
  • Enrique Becerril-Villanueva,
  • Samantha Alvarez-Herrera,
  • Lenin Pavón,
  • Luvia Sánchez-Torres,
  • Gabriel Gutiérrez-Ospina,
  • Manuel Iván Girón-Pérez,
  • Gabriela Damian-Morales,
  • Jesús Octavio Maldonado-Tapia,
  • Rubén López-Santiago,
  • Martha C. Moreno-Lafont

DOI
https://doi.org/10.3390/ph16111525
Journal volume & issue
Vol. 16, no. 11
p. 1525

Abstract

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Brucellosis infection causes non-specific symptoms such as fever, chills, sweating, headaches, myalgia, arthralgia, anorexia, fatigue, and mood disorders. In mouse models, it has been associated with increased levels of IL-6, TNF-α, and IFN-γ, a decrease in serotonin and dopamine levels within the hippocampus, induced loss of muscle strength and equilibrium, and increased anxiety and hopelessness. Imipramine (ImiP), a tricyclic antidepressant, is used to alleviate neuropathic pain. This study evaluated the effects of ImiP on Balb/c mice infected with Brucella abortus 2308 (Ba) at 14- and 28-days post-infection. Serum levels of six cytokines (IFN-γ, IL-6, TNF-α, IL-12, MCP-1. and IL-10) were assessed by FACS, while the number of bacteria in the spleen was measured via CFU. Serotonin levels in the hippocampus were analyzed via HPLC, and behavioral tests were conducted to assess strength, equilibrium, and mood. Our results showed that mice infected with Brucella abortus 2308 and treated with ImiP for six days (Im6Ba14) had significantly different outcomes compared to infected mice (Ba14) at day 14 post-infection. The mood was enhanced in the forced swimming test (FST) (p p p p p p p p p p p p p p < 0.0001). These findings suggest the potential for ImiP to be used as an adjuvant treatment for the symptoms of brucellosis, which requires future studies.

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