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 GSK3α/β 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 μL/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 GSK3α/β 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 GSK3α (Ser21) and GSK3β (Ser9) phosphorylation in mouse striatum. There was no significant alteration of GSK3α/β protein levels except for GSK3α 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 GSKα/β 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.