Trnecková Lenka, Armario Antonio, Hynie Sixtus, Sída Pavel, Klenerová Vera
Laboratory of Biochemical Neuropharmacology, Charles University in Prague, First Faculty of Medicine, Institute of Medical Biochemistry, Albertov 4, 128 00 Prague 2, Czech Republic.
Brain Res. 2006 Mar 10;1077(1):7-15. doi: 10.1016/j.brainres.2006.01.029. Epub 2006 Feb 20.
In order to study the contribution of genetic factors to the pattern of stress-induced brain activation, we studied the expression of c-fos mRNA, a marker of neuronal activity, in male Sprague-Dawley and Lewis strains, the latter being known to have a deficient responsiveness of the hypothalamic-pituitary-adrenal (HPA) axis. Immobilization (IMO) alone or combined with the immersion into water at 21 degrees C was applied for 15 or 60 min. The expression of c-fos mRNA was quantified by in situ hybridization in those brain areas that represent important parts of neuronal circuits activated by stress: medial prefrontal cortex, medial amygdala, lateral septum ventral part, paraventricular nucleus of the hypothalamus and locus coeruleus. While in controls, c-fos mRNA was not detectable in tested brain areas, both types of stressors induced a strong expression of this immediate early gene. There were only small differences in c-fos mRNA expression related to the type of stressor or the length of exposure to them. However, there were remarkable differences in the expression between the two rat strains. When compared to Sprague-Dawley rats, Lewis rats showed a reduced c-fos mRNA expression after both stressors in most brain areas, which may be related to the reduced responsiveness of HPA axis and also with other abnormal responses in this strain. However, this hyporesponsiveness was not observed in all brain areas studied, suggesting that there is not a generalized defective c-fos response to stress in Lewis rats and that some responses to stress may be normal in this strain.
为了研究遗传因素对应激诱导的脑激活模式的贡献，我们研究了雄性斯普拉格-道利大鼠和刘易斯大鼠神经元活动标志物c-fos mRNA的表达，已知后者下丘脑-垂体-肾上腺（HPA）轴反应性不足。单独固定（IMO）或与浸入21摄氏度水中相结合，持续15或60分钟。通过原位杂交对代表应激激活的神经回路重要部分的脑区进行c-fos mRNA表达定量：内侧前额叶皮质、内侧杏仁核、外侧隔腹侧部、下丘脑室旁核和蓝斑。在对照组中，受试脑区未检测到c-fos mRNA，而两种应激源均诱导了该即刻早期基因的强烈表达。与应激源类型或暴露于应激源的时间长度相关的c-fos mRNA表达只有微小差异。然而，两种大鼠品系之间的表达存在显著差异。与斯普拉格-道利大鼠相比，刘易斯大鼠在两种应激源后大多数脑区的c-fos mRNA表达均降低，这可能与HPA轴反应性降低以及该品系的其他异常反应有关。然而，在所有研究的脑区中均未观察到这种低反应性，这表明刘易斯大鼠对应激的c-fos反应并非普遍存在缺陷，且该品系对某些应激的反应可能是正常的。
