Major depression model induced by repeated and intermittent lipopolysaccharide administration: Long-lasting behavioral, neuroimmune and neuroprogressive alterations.

Abstract

Major depressed patients show increased bacterial translocation with elevated plasma levels of lipopolysaccharide (LPS), which may trigger immune-inflammatory and neuro-oxidative responses. Recently, an animal model based on chronic LPS administration was developed which was associated with long-lasting depressive-like and neuro-oxidative alterations in female mice. The aim of the current study was to investigate behavioral, neuroimmune and neuroprogressive alterations in female mice 6 weeks after LPS chronic exposure. Female mice received increasing doses of LPS during 5 days at one-month intervals repeated for 4 consecutive months. Six weeks after the last LPS-exposure, we assessed behavioral despair and anhedonia, microglial activation, alterations in tryptophan, 5-HT, kynurenine, quinolinic acid (QUIN) levels and spermidine/spermine N1-acetyltransferase (SAT1) expression in the hippocampus, both with and without fluoxetine administration. Our results show that six weeks post-LPS, mice present behavioral despair and anhedonia in association with increased IBA1 expression (a microglia activation marker), NF-kB p65 and IL-1β levels, indoleamine 2,3-dioxygenase (IDO1) mRNA expression, kynurenine, QUIN levels and QUIN/tryptophan ratio, and lowered tryptophan, 5-HT levels and SAT1 mRNA expression. Fluoxetine reversed the behavioral and neuroimmune alterations but had no effect in the reversal of IDO1 increased expression, QUIN levels and QUIN/tryptophan ratio. In conclusion, our results support the validity of the chronic LPS model of major depression and additionally shows its translational relevance with respect to neuroimmune and neuroprogressive pathways.

• Authors: Francisca Taciana Sousa Rodrigues, Marcos Romário Matos de Souza, Camila Nayane de Carvalho Lima, Francisco Eliclécio Rodrigues da Silva, Deiziane Viana da Silva Costa, Cláudio Costa Dos Santos, Fábio Miyajima, Francisca Cléa F de Sousa, Silvânia Maria Mendes Vasconcelos, Tatiana Barichello, João Quevedo, Michael Maes, David F de Lucena, Danielle Macedo
• Journal: Journal of psychiatric research (J Psychiatr Res) Vol. 107 Pg. 57-67 (12 2018) ISSN: 1879-1379 [Electronic] England
• PMID: 30326340 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Ltd. All rights reserved.

Chemical References

• Lipopolysaccharides
• Serotonin Uptake Inhibitors
• Fluoxetine
• Serotonin
• Tryptophan

Topics

• Animals
• Behavior, Animal (drug effects)
• Depressive Disorder, Major (chemically induced, drug therapy, immunology)
• Disease Models, Animal
• Female
• Fluoxetine (administration & dosage, pharmacology)
• Lipopolysaccharides (administration & dosage, pharmacology)
• Mice
• Serotonin (metabolism)
• Selective Serotonin Reuptake Inhibitors (administration & dosage, pharmacology)
• Tryptophan (drug effects)