Possible involvement of Interleukin-17A in the deterioration of prepulse inhibition on acoustic startle response in mice

Aim: Proinflammatory cytokines such as interleukin-6 (IL-6) and IL-17A have been implicated in the pathophysiology of schizophrenia which often shows sensorimotor gating abnormalities. This study aimed to examine whether a proinflammatory cytokine, IL-17A, induces impairment in sensorimotor gating in mice. We also examined whether IL-17A administration affects GSK3 alpha/beta protein level or phosphorylation in the striatum. Methods: Recombinant mouse IL-17A (low-dose: 0.5 ng/mL and high-dose: 50 ng/mL with 10 mu L/g mouse body weight, respectively) or vehicle was intraperitoneally administered into C57BL/6 male mice 10 times in 3 weeks (sub-chronic administration). Prepulse inhibition test using acoustic startle stimulus was conducted 4 weeks after the final IL-17A administration. We evaluated the effect of IL-17A administration on protein level or phosphorylation of GSK3 alpha/beta in the striatum by using Western blot analysis. Results: Administration of IL-17A induced significant PPI deterioration. Low-dose of IL-17A administration significantly decreased both GSK3 alpha (Ser21) and GSK3 beta(Ser9) phosphorylation in mouse striatum. There was no significant alteration of GSK3 alpha/beta protein levels except for GSK3 alpha in low-dose IL-17A administration group. Conclusion: We demonstrated for the first time that sub-chronic IL-17A administration induced PPI disruption and that IL-17A administration resulted in decreased phosphorylation of GSK alpha/beta at the striatum. These results suggest that IL-17A could be a target molecule in the prevention and treatment of sensorimotor gating abnormalities observed in schizophrenia.