Department of Psychological and Brain Sciences, University of Delaware, Newark, DE, United States of America.
PLoS One. 2018 Dec 7;13(12):e0205144. doi: 10.1371/journal.pone.0205144. eCollection 2018.
Glucocorticoid receptors (GRs) shuttle from the cytoplasm (cy) to the nucleus (nu) when bound with glucocorticoids (i.e. GR internalization) and alter transcriptional activity. GR activation within the fear circuit has been implicated in fear memory and post traumatic stress disorder (PTSD). However, no study to date has characterized GR internalization within the fear circuit during fear memory formation or examined how traumatic stress impacts this process. To address this, we assayed cy and nu GR levels at baseline and after auditory fear conditioning (FC) in the single prolonged stress (SPS) model of PTSD. Cy and nu GRs within the medial prefrontal cortex (mPFC), dorsal hippocampus (dHipp), ventral hippocampus (vHipp), and amygdala (AMY) were assayed using western blot. The distribution of GR in the cy and nu (at baseline and after FC) was varied across individual nodes of the fear circuit. At baseline, SPS enhanced cyGRs in the dHipp, but decreased cyGRs in the AMY. FC only enhanced GR internalization in the AMY and this effect was attenuated by SPS exposure. SPS also decreased cyGRs in the dHipp after FC. The results of this study suggests that GR internalization is varied across the fear circuit, which in turn suggests GR activation is selectively regulated within individual nodes of the fear circuit. The findings also suggest that changes in GR dynamics in the dHipp and AMY modulate the enhancing effect SPS has on fear memory persistence.
糖皮质激素受体（GRs）与糖皮质激素结合时从细胞质（cy）转移到细胞核（nu）（即 GR 内化），并改变转录活性。恐惧回路中的 GR 激活与恐惧记忆和创伤后应激障碍（PTSD）有关。然而，迄今为止，没有研究描述过在恐惧记忆形成过程中恐惧回路中 GR 的内化情况，也没有研究过创伤应激如何影响这一过程。为了解决这个问题，我们在 PTSD 的单延长应激（SPS）模型中，在听觉恐惧条件反射（FC）前后测定了基线和单延长应激（SPS）模型中的 cy 和 nu GR 水平。使用 Western blot 测定了内侧前额叶皮层（mPFC）、背侧海马（dHipp）、腹侧海马（vHipp）和杏仁核（AMY）中的 cy 和 nu GR。GR 在 cy 和 nu 中的分布（在基线和 FC 后）在恐惧回路的各个节点之间有所不同。在基线时，SPS 增强了 dHipp 中的 cyGR，但降低了 AMY 中的 cyGR。FC 仅增强了 AMY 中的 GR 内化，而 SPS 暴露则减弱了这种效应。SPS 还降低了 FC 后 dHipp 中的 cyGR。这项研究的结果表明，GR 内化在恐惧回路中是不同的，这反过来表明 GR 激活在恐惧回路的各个节点中是选择性调节的。研究结果还表明，dHipp 和 AMY 中 GR 动力学的变化调节了 SPS 对恐惧记忆持久性的增强效应。
