학술논문
Possible involvement of Interleukin‐17A in the deterioration of prepulse inhibition on acoustic startle response in mice
Document Type
Report
Author
Source
Neuropsychopharmacology Reports. September 2023, Vol. 43 Issue 3, p365, 8 p.
Subject
Language
English
Abstract
INTRODUCTION Accumulating evidence suggests that inflammatory cytokines are increased in the plasma of patients with psychiatric disorders including schizophrenia.[sup.1] Especially, it is well known that interleukin‐6 (IL‐6) concentration is increased [...]
: 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.
: 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.