Behavioural and neurochemical alterations following acute inflammation induced by intraperitoneal and intratracheal injection with lipopolysaccharide in mice.

The persistent symptoms of anxiety, depression, and fatigue that follow severe acute respiratory syndrome coronavirus 2 infection and accompany pulmonary inflammation pose significant clinical challenges. However, the correlation between pulmonary inflammation and mental health remains unclear. This study sought to examine the effects of intratracheal injection of lipopolysaccharide (LPS), a bacterial endotoxin, on anxiety-like behaviour in a mouse model suffering with pulmonary inflammation. The reactions of these animal models to new environments were evaluated using light-dark box and hole-board tests as anxiety-inducing stimuli. Microglial responses were evaluated via immunohistochemistry, and serum concentrations of tumour necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were measured. Both intraperitoneal and intratracheal injections of LPS induced anxiety-like behaviours, as indicated by the outcomes of the light-dark box and hole-board tests. Serum levels of TNF-α and IL-6 considerably increased following both injection routes. The protein levels of the 5-HT2A and 5-HT1A receptors, which are crucial for neuropsychological function, in the frontal cortex and hippocampus of mice remained unchanged following LPS injections. Notably, hippocampal levels of brain-derived neurotrophic factor (BDNF) remarkably decreased following LPS injections. In the lungs, the administration of LPS via the intratracheal route led to a significant rise in the number of white blood cells present in the bronchoalveolar lavage fluid compared to the intraperitoneal injection method. These findings suggest that inflammation induced by intratracheal LPS injection may lead to anxiety-like behaviours in mice, potentially involving mechanisms related to hippocampal BDNF expression, which contributes to anxiety after pulmonary inflammation.