Toll-like receptor 3 activation combined with INFα inhibits the expression of DISC1 in hippocampal neurons of mice

Abstract

Objective To explore the effect of Toll-like receptor 3 (TLR3) activation on the expression of neuronal disrupted-in-schizophrenia 1 (DISC1). Methods C57BL/6J mouse hippocampal neurons were incubated with polyI:C(1 μg/mL) or/and mIFNα(100 IU/mL) for 24 hrs. DISC1 mRNA and protein were detected by quantitive RT-PCR, immuno-cytochemistry staining and Western blot. The expression of STAT1, phospho-STAT1, p38 MAPK, phospho-p38 MAPK, GSK-3β, and phospho-GSK-3β was also detected by Western blot. Results Comparing with control group, the mRNA and protein expression of DISC1 in polyI:C group and IFNα group didn't show any changes, but significantly decreased with the co-stimulation by polyI:C and IFNα (P＜0.05). In addition, the phosphorylation of STAT1 was significantly increased in both IFNα group and co-stimulation group(P＜0.05) and the phosphorylation of p38 MAPK was elevated in polyI:C group and co-stimulation group (P＜0.05).The expression of GSK-3β and phospho-GSK-3β had no changes. Conclusions The combined stimulations of IFNα and TLR3 activation may inhibit the expression of DISC1 potentially through JAK/STAT1 and p38 MAPK signaling pathways.

Keywords

• disrupted-in-schizophrenia 1|toll-like receptor 3|interferon α|stat1|p38 mapk