Department of Cellular Biology, Physiology and Immunology, Institute of Neuroscience and Animal Physiology Unit, School of Biosciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain.
Eur J Neurosci. 2010 Jun;31(11):2043-52. doi: 10.1111/j.1460-9568.2010.07242.x.
Stress exposure resulted in brain induction of immediate-early genes (IEGs), considered as markers of neuronal activation. Upon repeated exposure to the same stressor, reduction of IEG response (adaptation) has been often observed, but there are important discrepancies in literature that may be in part related to the particular IEG and methodology used. We studied the differential pattern of adaptation of the IEGs c-fos and arc (activity-regulated cytoskeleton-associated protein) after repeated exposure to a severe stressor: immobilization on wooden boards (IMO). Rats repeatedly exposed to IMO showed reduced c-fos mRNA levels in response to acute IMO in most brain areas studied: the medial prefrontal cortex (mPFC), lateral septum (LS), medial amygdala (MeA), paraventricular nucleus of the hypothalamus (PVN) and locus coeruleus. In contrast, the number of neurons showing Fos-like immunoreactivity was only reduced in the MeA and the various subregions of the PVN. IMO-induced increases in arc gene expression were restricted to telencephalic regions and reduced by repeated IMO only in the mPFC. Double-labelling in the LS of IMO-exposed rats revealed that arc was expressed in only one-third of Fos+ neurons, suggesting two populations of Fos+ neurons. These data suggest that c-fos mRNA levels are more affected by repeated IMO than corresponding protein, and that arc gene expression does not reflect adaptation in most brain regions, which may be related to its constitutive expression. Therefore, the choice of a particular IEG and the method of measurement are important for proper interpretation of the impact of chronic repeated stress on brain activation.
应激暴露会导致大脑诱导即刻早期基因（IEGs），这些基因被认为是神经元激活的标志物。在反复暴露于相同应激源时，通常会观察到 IEG 反应的减少（适应），但文献中存在重要差异，这可能部分与所使用的特定 IEG 和方法有关。我们研究了反复暴露于严重应激源：木板固定（IMO）后 IEGs c-fos 和 arc（活性调节细胞骨架相关蛋白）的适应差异模式。反复暴露于 IMO 的大鼠在大多数研究的大脑区域中，急性 IMO 反应的 c-fos mRNA 水平降低：内侧前额叶皮质（mPFC）、外侧隔核（LS）、内侧杏仁核（MeA）、下丘脑室旁核（PVN）和蓝斑。相比之下，只有 MeA 和 PVN 的各个亚区中显示 Fos 样免疫反应的神经元数量减少。IMO 诱导的 arc 基因表达增加仅限于端脑区域，仅在 mPFC 中被反复 IMO 减少。暴露于 IMO 的 LS 大鼠的双重标记显示，arc 仅在三分之一的 Fos+神经元中表达，这表明存在两种 Fos+神经元群体。这些数据表明，c-fos mRNA 水平比相应的蛋白质更容易受到重复 IMO 的影响，而 arc 基因表达并不能反映大多数大脑区域的适应，这可能与其组成型表达有关。因此，特定 IEG 的选择和测量方法对于正确解释慢性重复应激对大脑激活的影响非常重要。
