The retrotransposition of L1 is involved in the reconsolidation of contextual fear memory in mice

Background: The long interspersed element-1 (LINE-1, L1) participates in memory formation, and DNA methylation patterns of L1 may suggest resilience or vulnerability factors for post-traumatic stress disorder (PTSD), of which the principal manifestation is a pathological exacerbation of fear memory. However, the unique roles of L1 in the reconsolidation of fear memory remain poorly understood. Objective: The present study investigated the roles of L1 in the reconsolidation of context-dependent fear memory. Methods: The current study used male mice obtained at two months of age. Mice underwent fear conditioning and fear recall in observation chambers. Fear memory was assessed by calculating the percentage of time spent freezing in a total of 5 min. The medial prefrontal cortex (mPFC) and hippocampus of the mice were removed and snap-frozen in nitrogen liquid for further analysis. Open Reading Frame 1 (ORF1) mRNA, and Open Reading Frame 2 (ORF2) mRNA of L1 were analyzed by Real-Time Quantitative Polymerase Chain Reaction. After the reactivation of fear memory, lamivudine was administered to inhibit L1 retrotransposition and its effects on fear memory reconsolidation were observed. Results: The expression of ORF1 and ORF2 mRNA in the mPFC and hippocampus after the recent (24 hours) and remote (14 days) fear memory recall exhibited an augmentation via different temporal and spatial patterns. The reconsolidation and spontaneous recovery of fear memory were markedly inhibited in mice administrated with lamivudine, which could block L1. The expression of DNA methyltransferase (Dnmt) mRNA was diminished following lamivudine treatment in the remote fear memory recall. Conclusions: The retrotransposition of L1 participated in the reconsolidation of fear memory after the reactivation of fear memory , and with lamivudine treatment, spontaneous recovery was decreased with time after the recent and remote fear memory recall, which might provide more clues for understanding the roles of L1 in fear memory and the possible strategy for treating PTSD.