Prolonged expression of zinc finger immediate-early gene mRNAs and decreased protein synthesis following kainic acid induced seizures
Prolonged expression of zinc finger immediate-early gene mRNAs and decreased protein synthesis following kainic acid induced seizures
复制标题
DOI：
10.1046/j.1460-9568.1999.00401.x
复制
发表时间：
1999-01-01
影响因子：
3.4
通讯作者：
Sharp, FR
中科院分区：
文献类型：
--
作者：
Honkaniemi, J;Sharp, FR
本研究采用原位杂交技术研究了红藻氨酸诱导癫痫发作对锌指即早基因NGFI-A、NGFI-B、NGFI-C、NGFI-2、NGFI-3和Nurr 1表达的影响。红藻氨酸显着诱导这些IEG，特别是在海马，皮层和杏仁核的30分钟。这种诱导逐渐减少，并在24小时在大多数地区恢复到基线。然而，在已知被红藻氨酸损伤的海马CA 1和CA 3亚区中，除IEGs-2外的所有IEGs的表达在24小时内保持升高。NGFI-A、NGFI-B、NGFI-C和较小程度的Nurr 1在颞叶皮质下区域也保持升高。到24小时，C-14-亮氨酸的掺入减少梨状皮质，杏仁核，并在CA 1和CA 3子域，但不是在CA 2和齿状回。这些地区显示减少蛋白质合成的海马24小时显示延长IEG诱导，而IEG表达恢复到控制水平的地区显示正常的蛋白质合成。在颞叶蛋白质合成减少与IEG表达减少共存，而在该地区附近的区域显示蛋白质合成减少IEG表达升高。蛋白质合成的减少局限于发生广泛神经元死亡的区域。这种在海马中的延长的IEG诱导，其与神经元死亡有关，可以仅代表由破坏的蛋白质合成引起的延长的mRNA周转。在颞叶中的延长的IEG表达似乎定位于细胞处于应激但仍然存活的区域。因此，持续的IEG表达可能代表神经元试图保护自己的应激反应，或者IEG反应可能是指示这些细胞启动导致程序性细胞死亡的途径的早期迹象。
In the present study in situ hybridization was used to study the effect of kainic acid induced seizures on the expression of the zinc finger immediate-early genes (IEGs) NGFI-A, NGFI-B, NGFI-C, egr-2, egr-3 and Nurr1. Kainic acid markedly induced these IEGs especially in hippocampus, cortex and amygdala by 30 min. This induction gradually decreased and returned to baseline by 24 h in most regions. However, in the CA1 and CA3 subfields of hippocampus known to be damaged by kainic acid the expression of all the IEGs except egr-2 remained elevated for 24 h. NGFI-A, NGFI-B, NGFI-C and to a lesser extent, Nurr1, remained elevated also in the subcortical region of the temporal lobe. By 24 h incorporation of C-14-leucine decreased in the piriform cortex, amygdala, and in the CA1 and CA3 subfields, but not in CA2 and dentate gyrus. These areas showing decreased protein synthesis in the hippocampus by 24 h showed prolonged IEG induction, whereas IEG expression returned to control levels in areas showing normal protein synthesis. In the temporal lobe decreased protein synthesis coexisted with decreased IEG expression, whereas areas in the vicinity of the region showing decreased protein synthesis demonstrated elevated IEG expression. The decreased protein synthesis was localized in areas where extensive neuronal death has occurred. This prolonged IEG induction in the hippocampus, which has been linked with neuronal death, could solely represent a prolonged mRNA turnover caused by disrupted protein synthesis, The prolonged IEG expression in the temporal lobe appeared to be localized in regions where the cells are in stress, but still viable. The sustained IEG expression might therefore either represent a stress response by which the neurons are trying to protect themselves or, alternatively, the IEG response may be an early sign indicating that these cells are initiating a pathway leading to programmed cell death.