Toll-like receptor 7-mediated enhancement of contextual fear memory in mice |
| |
Authors: | Kubo Yasunori Yanagawa Yoshiki Matsumoto Machiko Hiraide Sachiko Kobayashi Masanobu Togashi Hiroko |
| |
Institution: | a Department of Pharmacology, Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japanb Fundamental Health Sciences, School of Nursing and Social Sciences, Health Sciences University of Hokkaido, Japan |
| |
Abstract: | 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. |
| |
Keywords: | Toll-like receptor 7 Contextual fear memory Type I interferon Imiquimod |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|