Department of Psychiatry and Behavioral Neuroscience, Wayne State University School of Medicine, Detroit, MI, USA.
Neurosci Res. 2013 Feb;75(2):130-7. doi: 10.1016/j.neures.2012.11.001. Epub 2012 Nov 29.
Animal models of posttraumatic stress disorder (PTSD) can explore neurobiological mechanisms by which trauma enhances fear and anxiety reactivity. Single prolonged stress (SPS) shows good validity in producing PTSD-like behavior. While SPS-induced behaviors have been linked to enhanced glucocorticoid receptor (GR) expression, the molecular ramifications of enhanced GR expression have yet to be identified. Phosphorylated protein kinase B (pAkt) is critical for stress-mediated enhancement in general anxiety and memory, and may be regulated by GRs. However, it is currently unknown if pAkt levels are modulated by SPS, as well as if the specificity of GR and pAkt related changes contribute to anxiety-like behavior after SPS. The current study set out to examine the effects of SPS on GR and pAkt protein levels in the amygdala and hippocampus and to examine the specificity of these changes to unconditioned anxiety-like behavior. Levels of GR and pAkt were increased in the hippocampus, but not amygdala. Furthermore, SPS had no effect on unconditioned anxiety-like behavior suggesting that generalized anxiety is not consistently observed following SPS. The results suggest that SPS-enhanced GR expression is associated with phosphorylation of Akt, and also suggest that these changes are not related to an anxiogenic phenotype.
创伤后应激障碍（PTSD）的动物模型可以探索创伤增强恐惧和焦虑反应的神经生物学机制。单一延长应激（SPS）在产生类似 PTSD 的行为方面具有良好的有效性。虽然 SPS 诱导的行为与增强糖皮质激素受体（GR）表达有关，但增强 GR 表达的分子后果尚未确定。磷酸化蛋白激酶 B（pAkt）对于应激介导的一般焦虑和记忆增强至关重要，并且可能受到 GR 的调节。然而，目前尚不清楚 SPS 是否调节 pAkt 水平，以及 GR 和 pAkt 相关变化的特异性是否有助于 SPS 后的焦虑样行为。本研究旨在检查 SPS 对杏仁核和海马体中 GR 和 pAkt 蛋白水平的影响，并检查这些变化对非条件性焦虑样行为的特异性。GR 和 pAkt 水平在海马体中增加，但在杏仁核中没有增加。此外，SPS 对非条件性焦虑样行为没有影响，这表明 SPS 后并不总是观察到广泛性焦虑。结果表明，SPS 增强的 GR 表达与 Akt 的磷酸化有关，并且还表明这些变化与焦虑表型无关。
