School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
School of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
Biochem Biophys Res Commun. 2020 Feb 26;523(1):86-90. doi: 10.1016/j.bbrc.2019.12.038. Epub 2019 Dec 9.
Fear renewal is defined as return of the conditioned fear responses after extinction when a conditioned stimulus (CS) is given outside of the extinction context. Previously, we have suggested that extinction induces S-nitrosylation of GluA1 in the lateral amygdala (LA), and that the extinction-induced S-nitrosylation of GluA1 lowers the threshold of GluA1 phosphorylation (at Ser 831) which is required for fear renewal. This fits nicely with the fact that fear renewal is induced by weak stimuli. However, it has not been tested whether S-nitrosylation of GluA1 in the LA is indeed required for fear renewal. In the present study, we used three different chemicals to impede protein S-nitrosylation via distinct mechanisms. Fear renewal was inhibited by microinjection of 7-Nitroindazole (nNOS inhibitor), and ZL006 (a blocker of PSD-95-nNOS interaction) before fear renewal. Furthermore, fear renewal was also attenuated by microinjection of a strong antioxidant (N-acetyl cysteine), which scavenges reactive oxygen including nitric oxide, into the LA before each extinction training. These findings suggest that protein S-nitrosylation is required for fear renewal.
恐惧再现被定义为在条件刺激（CS）在 extinction 环境之外给予时，条件反射性恐惧反应的回归。先前，我们已经表明，extinction 会诱导外侧杏仁核（LA）中 GluA1 的 S-亚硝基化，而 GluA1 的 extinction 诱导的 S-亚硝基化会降低 GluA1 磷酸化（在 Ser 831 处）的阈值，这对于恐惧再现是必需的。这与恐惧再现是由弱刺激诱导的事实非常吻合。然而，尚未测试 LA 中的 GluA1 的 S-亚硝基化是否确实是恐惧再现所必需的。在本研究中，我们使用了三种不同的化学物质，通过不同的机制来阻碍蛋白质的 S-亚硝基化。在恐惧再现之前，通过微注射 7-硝基吲唑（nNOS 抑制剂）和 ZL006（PSD-95-nNOS 相互作用的阻断剂）来抑制恐惧再现。此外，在每次 extinction 训练之前，将强抗氧化剂（N-乙酰半胱氨酸）微注射到 LA 中，也可以减弱恐惧再现。这些发现表明，蛋白质 S-亚硝基化是恐惧再现所必需的。
