Repeated low doses of lipopolysaccharide exacerbate behavioral changes induced by social isolation.

Publication date: Jul 13, 2025

Social isolation (SI) due to Coronavirus disease 2019 had a substantial impact on mental health, increasing cases of major depressive disorder (MDD) and anxiety. Young individuals are notably affected, as research indicates that inflammatory responses can trigger mental health disorders, with chronic stress worsening this effect. Thus, the primary objective of this study was to investigate the combination of SI with repeated low doses of an inflammation inducer in young mice on behavioral and molecular changes in adulthood. For this, young Swiss male mice were housed in groups or isolated and administered intraperitoneally either low doses of lipopolysaccharide (LPS) or saline for 6 weeks. In the seventh week, behavioral tests were carried out. Another cohort of animals, at the end of the 6-week experimental protocol, was subjected to the restraint stress challenge (RSC) before behavioral tests. Our results suggest that the SI disrupts the animal’s self-grooming and memory, in addition to inducing an anxiety-related behavioral phenotype and increasing the expression of transient receptor potential ankyrin 1 (TRPA1) in the hippocampus. On the other hand, the LPS administration triggered despair-like behavior accompanied by an increase in hippocampal microglial activation. When SI and LPS were combined, the behavioral changes were added. Concerning RSC, in general, it reversed most of the changes induced by the protocols. In this way, it can be concluded that repeated administration of low doses of LPS in young mice housed alone induced behavioral changes in different features observed in MDD.

Semantics