CircTmeff-1 in the nucleus accumbens regulates the reconsolidation of cocaine-associated memory
CircTmeff-1 in the nucleus accumbens regulates the reconsolidation of cocaine-associated memory
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伏隔核中的 CircTmeff-1 调节可卡因相关记忆的重新巩固
DOI：
10.1016/j.brainresbull.2022.04.010
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发表时间：
2022-04
期刊：
影响因子：
--
通讯作者：
Chunling Ma
中科院分区：
文献类型：
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作者：
Qianchao Shen;Bing Xie;Ewa Galaj;Hailei Yu;Xiaojie Li;Yun Lu;Minglong Zhang;Di Wen;Chunling Ma
药物记忆的重新巩固是在无条件（UCS;例如，药物）或条件刺激（CS;例如，药物配对环境），并为预防药物复发提供了希望。环状RNA（circRNA）在基因表达的转录和转录后调控中具有重要作用。然而，circRNA在药物记忆再巩固中的作用尚不清楚。在这里，我们观察到，可卡因诱导的记忆检索显着增加circTmeff-1水平的核延髓（NAc）的核心，但不是壳。重要的是，在NAc核心中使用病毒破坏circTmeff-1的表达破坏了可卡因相关记忆的重新巩固。在NAc壳中或在没有UCS回收的情况下或在UCS回收后9小时敲低circTmeff-1没有这种效果。从机制上讲，使用生物信息学分析和功能丧失或获得测定，我们揭示了在可卡因相关记忆的再巩固期间，EschomiR-206逆转了circTmeff-1敲低对脑源性神经营养因子（BDNF）表达的抑制作用。综上所述，这些结果证明了circTmeff-1在可卡因相关记忆的再巩固中的作用，并且circTmeff-1可能作为miR-206的诱饵来调节BDNF的表达。·UCS回收增加了NAc核心而非外壳中的circTmeff-1表达。·敲低circTmeff-1会损害UC诱导的记忆再巩固。· Circtmeff-1调节miR-206和BDNF的表达。
Reconsolidation of drug memories is the process of restoring unstable memories after unconditioned (UCS; e.g., drugs) or conditioned stimulus (CS; e.g., drug-paired contexts), and provides promise for prevention of drug relapse. Circular RNAs (circRNAs) have important effects on the transcription and post-transcriptional regulation of gene expression. However, the role of circRNAs in the reconsolidation of drug memories is unclear. Here, we observed that cocaine-induced memory retrieval significantly increased circTmeff-1 level in the nucleus accumbens (NAc) core but not shell. Importantly, the disrupted expression of circTmeff-1 using virus in the NAc core damaged the reconsolidation of cocaine-associated memories. The knockdown of circTmeff-1 in the NAc shell or without UCS retrieval or 9 h after UCS retrieval had no such effects. Mechanistically, using bioinformatic analysis and loss- or gain- of function assays, we revealed that antagomiR-206 reversed the inhibitory effect of circTmeff-1 knockdown on the expression of brain-derived neurotrophic factor (BDNF) during the reconsolidation of cocaine-associated memories. Taken together, these results demonstrate the role of circTmeff-1 in the reconsolidation of cocaine-associated memory and that circTmeff-1 may function as a decoy for miR-206 to regulate the expression of BDNF. • The UCS retrieval increased circTmeff-1 expression in the NAc core but not shell. • Knockdown of circTmeff-1 damages UCS-induced reconsolidation of memory. • Circtmeff-1 regulates the expression of miR-206 and BDNF.