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

机译：Toll样受体7介导的小鼠情境恐惧记忆的增强

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摘要

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 15 h before contextual fear conditioning. Imiquimod treatment 4 or 15 h before fear conditioning significantly enhanced context-dependent freezing behavior. This imiquimod-induced enhancement of fear-related behaviors was observed 120 h 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 2 h after imiquimod treatment. Imiquimod also increased interleukin (IL)-1β mRNA expression in the brain at 4 h following administration, while mRNA expression of F4/80, 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.
机译：Toll样受体（TLR）7识别病毒单链RNA，并触发I型干扰素（IFN）IFN-α和IFN-β的产生。咪喹莫特（一种合成的TLR7配体）诱导产生I型干扰素，并在临床上用作抗病毒和抗肿瘤药物。在本研究中，我们检查了咪喹莫特对小鼠条件性和先天性恐惧行为的影响。咪喹莫特在情境恐惧调节之前的2、4或15小时服用。恐惧调节前4或15小时的咪喹莫特治疗显着增强了情景相关的冻结行为。恐惧调节后120小时观察到了这种咪喹莫特诱导的恐惧相关行为的增强。相反，咪喹莫特不能增强TLR7基因敲除小鼠的背景依赖性冻结行为。咪喹莫特对疼痛阈值或与先天性恐惧相关的行为没有显着影响，用升高的迷宫来衡量。咪喹莫特治疗后2小时，大脑中I型IFN mRNA的水平显着增加。咪喹莫特也可在给药后4小时增加大脑中白介素（IL）-1βmRNA的表达，而巨噬细胞标记物F4 / 80的mRNA表达不受咪喹莫特治疗的影响。我们的发现表明，TLR7介导的信号传导可能通过诱导脑中I型IFN和IL-1β的表达来增强小鼠的情境恐惧记忆。

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