de Kloet E Ron, Joëls Marian, Holsboer Florian
Department of Medical Pharmacology, Leiden Amsterdam Center for Drug Research and Leiden University Medical Center, Gorlaeus Laboratories, Leiden University, PO Box 9502, 2300 RA Leiden, The Netherlands.
Nat Rev Neurosci. 2005 Jun;6(6):463-75. doi: 10.1038/nrn1683.
In response to stress, the brain activates several neuropeptide-secreting systems. This eventually leads to the release of adrenal corticosteroid hormones, which subsequently feed back on the brain and bind to two types of nuclear receptor that act as transcriptional regulators. By targeting many genes, corticosteroids function in a binary fashion, and serve as a master switch in the control of neuronal and network responses that underlie behavioural adaptation. In genetically predisposed individuals, an imbalance in this binary control mechanism can introduce a bias towards stress-related brain disease after adverse experiences. New candidate susceptibility genes that serve as markers for the prediction of vulnerable phenotypes are now being identified.
作为对压力的反应，大脑会激活多个分泌神经肽的系统。这最终会导致肾上腺皮质类固醇激素的释放，这些激素随后会反馈到大脑并与两种作为转录调节因子的核受体结合。通过作用于许多基因，皮质类固醇以二元方式发挥作用，并作为控制行为适应基础的神经元和网络反应的主开关。在有遗传易感性的个体中，这种二元控制机制的失衡会在经历不良事件后导致偏向于应激相关脑部疾病的倾向。目前正在确定作为预测易患表型标志物的新候选易感基因。
