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Toll-like receptor 7-mediated enhancement of contextual fear memory in mice

submitted by dallvit 1 year and 11 months ago
Toll-like receptor (TLR) 7 recognizes viral single-stranded RNA and triggers production of the type I interferons (IFNs) IFN-α and IFN-β. Imiquimod, a synthetic TLR7 ligand, induces production of type I IFNs and is used clinically as an antiviral and antitumor drug. In the present study, we examined the effect of imiquimod on conditioned and innate fear behaviors in mice. Imiquimod was administered 2, 4, or 15h before contextual fear conditioning. Imiquimod treatment 4 or 15h before fear conditioning significantly enhanced context-dependent freezing behavior. This imiquimod-induced enhancement of fear-related behaviors was observed 12h after fear conditioning. In contrast, imiquimod failed to enhance context-dependent freezing behavior in TLR7 knockout mice. Imiquimod had no significant effect on pain threshold or on innate fear-related behavior, as measured by the elevated plus-maze. The levels of type I IFN mRNA in the brain were significantly increased at 2h after imiquimod treatment. Imiquimod also increased interleukin (IL)-1β mRNA expression in the brain at 4h following administration, while mRNA expression of F4/8, a macrophage marker, was unaffected by imiquimod treatment. Our findings suggest that TLR7-mediated signaling enhances contextual fear memory in mice, possibly by inducing the expression of type I IFNs and IL-1β in the brain. Imiquimod, a synthetic TLR7 ligand, enhances context-dependent freezing behavior. TLR7 deficiency abolished the effect of imiquimod on freezing behavior. TLR7 may be involved in the regulation of defensive behavior.


Topic: Health

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