Effects of intracerebroventricular lipopolysaccharide administration on behavioral, neurochemical, and neurogenomic responses in adult zebrafish

Abstract

Neuroinflammation is a common trigger of multiple neuropsychiatric disorders. Lipopolysaccharide (LPS) administration is widely used to induce systemic and neural inflammation in various in vivo animal models. Complementing rodent studies, the zebrafish emerges as a powerful model organism for studying complex neurobehavioral consequences of neuroinflammation. Here, adult fish received an intracerebroventricular injection of LPS and were assessed behaviorally in the novel tank, the zebrafish tail immobilization (ZTI) and the Y-maze tests for locomotor, affective and cognitive responses. We also performed neurochemical and neurogenomic profiling of zebrafish to assess their brain monoamine levels and the expression of selected cytokine-related genes. Overall, LPS-treated zebrafish showed hypolocomotion in the novel tank test, reduced spontaneous alternation in the Y-maze and higher ZTI test immobility, suggesting affective and cognitive deficits, accompanied by elevated serotonin turnover and upregulated pro-inflammatory (Il1b, tnf) and anti-inflammatory (il10) cytokine genes. Collectively, these findings parallel rich rodent evidence of central LPS effects, and support zebrafish as a valuable model system for probing the interplay between neuroinflammation and psychiatric disorders, with a specific focus on evolutionarily conserved, shared mechanisms of CNS pathogenesis.