• Elisa Piton Lovis, Gabriele Cheiran Pereira, Fernanda Tibolla Viero, Francini Arboit, Leonardo Guedes de Andrade, Gabriela Becker, Maria Fernanda Pessano Fialho, Evelyne da Silva Brum, José Eduardo de Souza Ferreira, Eliane Maria Zanchet, Valerio Valdetar Marques Portela Junior, Gabriela Trevisan Dos Santos, Sara Marchesan Oliveira, Micheli Mainardi Pillat, and Guilherme Vargas Bochi.
• Center of Health Sciences, Department of Physiology and Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil; Center of Health Sciences, Postgraduate Program in Pharmacology, Federal University of Santa Maria, Santa Maria, RS, Brazil.
• Neuroscience. 2025 Feb 16; 567: 281293281-293.

AbstractMajor depressive disorder (MDD) is a complex neuropsychiatric disorder potentially influenced by factors such as stress and inflammation. Chronic stress can lead to maladaptive brain changes that may trigger immune hyperactivation, contributing to MDD's pathogenesis. While the involvement of inflammation in MDD is well established, the effects of inflammatory preconditioning in animals subsequently exposed to chronic stress remain unclear. This study aimed to investigate the impact of inflammatory preconditioning on behavioral, biochemical, and molecular changes in adult male Swiss mice subjected to chronic restraint stress (CRS). The mice received a single injection of lipopolysaccharide (LPS) 24 h before thefirst CRS and performed 6 h daily for 28 days. Behavioral tests were conducted 24 h after the last CRS, across 4 days, and euthanasia followed 24 h after the final tests. Results indicated that only the LPS + CRS group exhibited depressive- and anxiety-like behaviors, accompanied by demotivation and apathy. Biochemical and molecular analyses revealed anoxidative imbalance in the hippocampus, marked by elevated H2O2 levels and MPO activity. In the prefrontal cortex, theLPS + CRS group demonstrated a central inflammatory imbalance, with reduced IL-10 levels, increased Iba1 gene expression, and decreased Gfap and Bdnf gene expression. A trend toward elevated IL-17 levels was also observed at the peripheral level. These findings indicate that inflammatory preconditioning contributes significantly to behaviors phenotypically associated with MDD. Furthermore, the study suggests that these behavioral changes are linked to a dysfunctional immune response and impaired neuroplasticity.Copyright © 2024 International Brain Research Organization (IBRO). Published by Elsevier Inc. All rights reserved.

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