Nelovkov Aleksei, Areda Tarmo, Innos Jürgen, Kõks Sulev, Vasar Eero
Department of Physiology, University of Tartu, Biomedicum, 19 Ravila Street, 51014 Tartu, Estonia.
Brain Res. 2006 Jul 19;1100(1):21-31. doi: 10.1016/j.brainres.2006.05.007.
The aim of the present study was to evaluate the expression of genes in relation to the exploratory activity of rats. Limbic system-associated membrane protein (LsAMP) gene, gamma-aminobutyric acid-(GABA)- and cholecystokinin-(CCK)-related genes were analyzed in the frontal cortex, amygdala and periaqueductal gray (PAG) after exposure of rats to exploratory challenge. Two groups of animals displaying low and high exploratory activity in the elevated plus-maze were selected for gene expression studies from the population of 43 male Wistar rats. Eight rats were taken randomly from the same cages as animals exposed to the plus-maze, but they were not subjected to the exploratory test. This home-cage control group was also used for gene expression analysis in order to explore a possible impact of the plus-maze exposure. Rats with low and high exploratory activity displayed clearly distinct profiles in gene expression. Most prominent alterations were established in the amygdala where almost all GABA-related and CCK receptor genes were two- to five-fold up-regulated in low exploratory activity rats compared to high exploratory activity and home-cage control group. The expression of several GABA-related genes was also increased in the PAG of animals displaying low exploratory activity compared to the other groups. Moreover, we found reduced expression of GABA- and CCK-related genes in all three brain regions in animals with high exploratory activity compared to the home-cage control group. In addition to these findings, we established a significantly increased expression of the LsAMP gene in the amygdala and PAG of low exploratory activity animals compared with the other groups. In conclusion, low and high exploratory activity rats differed not only by their exploratory activity but also displayed opposite gene expression patterns. Low exploratory activity of rats correlated with the up-regulation of LsAMP and GABA-related genes in the amygdala and PAG and with the up-regulation of CCK receptors in the amygdala. High exploratory activity of rats was related to a significant down-regulation of CCK receptor genes in the amygdala and PAG. These rats also displayed the reduced expression of GABA-related genes in the frontal cortex and PAG.
本研究的目的是评估与大鼠探索活动相关的基因表达。在大鼠经受探索性挑战后，分析其额叶皮质、杏仁核和导水管周围灰质（PAG）中与边缘系统相关膜蛋白（LsAMP）基因、γ-氨基丁酸（GABA）和胆囊收缩素（CCK）相关的基因。从43只雄性Wistar大鼠群体中，选择在高架十字迷宫中表现出低探索活动和高探索活动的两组动物进行基因表达研究。从与暴露于十字迷宫的动物相同的笼子中随机选取8只大鼠，但它们未接受探索性测试。这个笼内对照组也用于基因表达分析，以探究十字迷宫暴露可能产生的影响。低探索活动和高探索活动的大鼠在基因表达上表现出明显不同的特征。最显著的变化发生在杏仁核，与高探索活动组和笼内对照组相比，几乎所有与GABA相关的基因和CCK受体基因在低探索活动大鼠中上调了2至5倍。与其他组相比，在表现出低探索活动的动物的PAG中，几种与GABA相关的基因表达也增加了。此外，与笼内对照组相比，我们发现高探索活动动物的所有三个脑区中与GABA和CCK相关的基因表达均降低。除了这些发现，我们还发现与其他组相比，低探索活动动物的杏仁核和PAG中LsAMP基因的表达显著增加。总之，低探索活动和高探索活动的大鼠不仅在探索活动上存在差异，而且表现出相反的基因表达模式。大鼠的低探索活动与杏仁核和PAG中LsAMP和GABA相关基因的上调以及杏仁核中CCK受体的上调相关。大鼠的高探索活动与杏仁核和PAG中CCK受体基因的显著下调有关。这些大鼠在额叶皮质和PAG中还表现出与GABA相关基因表达的降低。
