Intermittent Hypoxia Exacerbates Lipopolysaccharide-Induced Neurobehavioral Abnormalities: The Role of Neuroinflammation and Synaptic-Related Proteins.

BACKGROUND

Sepsis is a common systemic inflammatory disease clinically observed in patients with severe trauma or infectious diseases. Lipopolysaccharide (LPS) serves as a classic tool for studying infection-related neuroinflammation and behavioral changes. Research indicates that LPS can induce peripheral inflammation and neuroinflammation, leading to synaptic dysfunction and neurobehavioral abnormalities. Furthermore, studies suggest that stress can increase susceptibility to inflammation. Intermittent hypoxia, a core pathological feature of obstructive sleep apnea syndrome, induces low-grade chronic inflammation in the central nervous system.

OBJECTIVE

This study investigates whether intermittent hypoxia exacerbates LPS-induced cognitive impairment, depression, and anxiety-like behaviors, and explores its potential mechanisms.

METHODS

Adult mice were treated with LPS alone or in combination with daily 8-h intermittent hypoxia via a hypoxia chamber. Depression and anxiety-like behavior were assessed using the tail suspension, forced swim, elevated plus maze, and open field tests. Spatial learning and memory were measured using the Morris water maze test. Pro-inflammatory cytokines and levels of genes and proteins of synaptic-related proteins were detected using enzyme-linked immunosorbent assay, western blotting, and real-time fluorescence-based quantitative PCR, respectively.

RESULTS

LPS-induced impaired cognitive function, increased depression-like and anxiety-like behaviors, elevated pro-inflammatory cytokines, and decreased mRNA and protein levels of synapse-related proteins, synaptosomal-associated protein of 25 kDa, synaptotagmin-1, synaptophysin, and postsynaptic density protein-95 in adult male mice. Intermittent hypoxia exacerbated these adverse effects.

CONCLUSION

Intermittent hypoxia exacerbates LPS-induced neurobehavioral abnormalities, which are associated with neuroinflammation and alterations in synapse-related proteins.