The acute effects of antimicrobials and lipopolysaccharide on the cellular mechanisms associated with neurodegeneration in pubertal male and female CD1 mice

Exposure to stressors during puberty can cause enduring effects on brain functioning and behaviours related to neurodegeneration. However, the mechanisms underlying these effects remain unclear. The gut microbiome is a complex and dynamic system that could serve as a possible mechanism through which early life stress may increase the predisposition to neurodegeneration. Therefore, the current study was designed to examine the acute effects of pubertal antimicrobial and lipopolysaccharide (LPS) treatments on the cellular mechanisms associated with neurodegenerative disorders in male and female mice. At five weeks of age, male and female CD-1 mice received 200 μL of broad-spectrum antimicrobials or water, through oral gavage, twice daily for seven days. Mice received an intraperitoneal (i.p.) injection of either saline or LPS at 6 weeks of age (i.e., pubertal period). Sickness behaviours were recorded and mice were euthanized 8 h post-injection. Following euthanasia, brains and blood samples were collected. The results indicated that puberal antimicrobial and LPS treatment induced sex-dependent changes in biomarkers related to sickness behaviour, peripheral inflammation, intestinal permeability, and neurodegeneration. The findings suggest that pubertal LPS and antimicrobial treatment may increase susceptibility to neurodegenerative diseases later in life, particularly in males.