Enhanced Depressive-like Behaviors after Toll-like Receptor 7 Stimulation in Mice

摘要

Toll-like receptor (TLR) 7 recognizes viral single-stranded RNA and triggers anti-viral immune responses through the production of type I interferons (IFNs) IFN-a and IFN-p. IFN-a is known to induce various psychiatric changes such as depressive symptoms; however, the correlation with TLR7 activation remains to be determined. In this study, we examined the effect of imiquimod, a TLR7 specific ligand, on depressive-like behaviors evaluated by the forced swim test (FST) and the tail suspension test (TST) in mice. Immobility durations were significantly prolonged in both FST and TST by 2 h after imiquimod treatment (50 |ag/body， i.p.)， indicating that TLR7 activation enhanced depressive-like behaviors in mice. In addition, imiquimod induced IFN-a mRNA expression in the hippocampus, whereas it prevented long-term potentiation in the Schaffer-CAl pathway (i.e., hippocampal synaptic plasticity). Moreover, TLR7 mRNA expression in the hippocampus was higher than that in the whole brain. These findings suggest that TLR7 activation enhances depressive-like behaviors in mice, possibly through increasing IFN-a expression and altering synaptic plasticity in the hippocampus.