Abstract # 2073 Cytokine expression and sickness behavior following lipopolysaccharide stimulation in the Fmr1 knockout mouse

Abstract

Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by a single genetic mutation in the Fragile X mental retardation 1 (FMR1) gene. In addition to behavioral and physiological symptoms, evidence has suggested that individuals with FXS may have altered immune function. In the present study, we investigated how Fmr1 knockout (KO) mice would respond to an innate immune stimulus by administering a single injection of the bacterial mimetic lipopolysaccharide (LPS) (0.33mg/kg, i.p.) or 0.9% physiological saline. Four hours after injections, brains were dissected, followed by RNA isolation and qRT-PCR on hippocampal tissue. As expected, we found LPS significantly increased proinflammatory cytokines in Fmr1 KO and wild type (WT) mice (IL-1beta, TNF-alpha, IL-6, MCP-1), with no effect on anti-inflammatory cytokine IL-10. Additionally, Fmr1 KO mice given LPS had trending elevations in proinflammatory cytokine expression compared to WT LPS mice. A separate cohort of mice were tested in a burrowing paradigm with a single injection of LPS or saline prior to the testing phase, however, no differences were detected between genotypes in the behavioral sickness response following an immune stimulus. Twenty-four hours following injections, we examined cytokine expression again to determine whether differences detected at 4hr. post-LPS injections were similarly altered at 24hrs. This study provides insight into whether dysregulated immunity could be playing a broader role in the pathophysiology of FXS.