Lin T N, Chen J J, Wang S J, Cheng J T, Chi S I, Shyu A B, Sun G Y, Hsu C Y
Division of Neuroscience, Academia Sinica, Taipei, Taiwan, ROC.
Brain Res Mol Brain Res. 1996 Dec 31;43(1-2):149-56. doi: 10.1016/s0169-328x(96)00169-6.
Cerebral ischemia is known to induce the expression of several immediate early genes (IEGs), including c-fos and c-jun, which subsequently regulate a number of late effector genes. In this study, we examined the expression of NGFI-B (or nur 77) mRNA in a rat focal cerebral ischemia-reperfusion model. NGFI-B is a member of the IEGs which encodes for a nuclear receptor and is rapidly induced by nerve growth factor (NGF). Northern blot analysis showed a rapid but transient enhancement of NGFI-B mRNA, a peak level for which was observed at 30 min of reperfusion following 60 min ischemic insult. At the peak level, quantitative analysis of the blot indicated a 12-fold and 4-fold increase of NGFI-B mRNA in the ischemic cortex and ipsilateral hippocampus, respectively, as compared to the sham-operated control. No apparent changes in mRNA levels were observed within contralateral sites of the cortex. Results from in situ hybridization showed that severe ischemia (60 min) resulted in a marked increase of NGFI-B mRNA throughout the entire ischemic cerebral cortex. The increase was particularly notable in the frontal, occipital, perirhinal and piriform cortical regions and in the dentate gyrus and CAI-3 regions of the ipsilateral hippocampus. A marked induction was also noted in the ipsilateral caudate putamen. Unlike the induction profile of NGFI-B mRNA, severe ischemia resulted in bilateral increases of its family gene, NGFI-A mRNA. The spatial induction profile is similar to that of NGFI-B mRNA in both hemispheres, except within the region of the contralateral dentate gyrus which showed low levels of NGFI-A mRNA. The expression pattern of NGF and BDNF mRNA, upstream genes of NGFI-B, were also examined. Interestingly the temporal and spatial expression patterns of BDNF mRNA were very similar to that of NGFI-A mRNA under the same conditions, whereas increased NGF and NGFI-B mRNA were observed only in the ipsilateral hemisphere. It is likely that multiple and/or overlapping pathways are activated subsequent to ischemic challenge which in turn are crucial for cel survival and/or functional recovery following focal cerebral ischemia.
已知脑缺血可诱导包括c-fos和c-jun在内的多种即刻早期基因（IEGs）的表达，这些基因随后会调节许多晚期效应基因。在本研究中，我们在大鼠局灶性脑缺血再灌注模型中检测了NGFI-B（或nur 77）mRNA的表达。NGFI-B是IEGs的成员之一，编码一种核受体，并被神经生长因子（NGF）快速诱导。Northern印迹分析显示NGFI-B mRNA迅速但短暂增强，在60分钟缺血损伤后再灌注30分钟时观察到其峰值水平。在峰值水平时，印迹的定量分析表明，与假手术对照组相比，缺血皮层和同侧海马体中NGFI-B mRNA分别增加了12倍和4倍。在皮层的对侧部位未观察到mRNA水平的明显变化。原位杂交结果显示，严重缺血（60分钟）导致整个缺血性脑皮层中NGFI-B mRNA显著增加。这种增加在额叶、枕叶、嗅周和梨状皮质区域以及同侧海马体的齿状回和CAI-3区域尤为明显。在同侧尾状壳核中也观察到明显的诱导。与NGFI-B mRNA的诱导情况不同，严重缺血导致其家族基因NGFI-A mRNA双侧增加。空间诱导模式在两个半球中与NGFI-B mRNA相似，除了对侧齿状回区域显示NGFI-A mRNA水平较低。还检测了NGFI-B的上游基因NGF和BDNF mRNA的表达模式。有趣的是，在相同条件下，BDNF mRNA的时空表达模式与NGFI-A mRNA非常相似，而仅在同侧半球观察到NGF和NGFI-B mRNA增加。缺血挑战后可能激活了多种和/或重叠的途径，这些途径反过来对于局灶性脑缺血后的细胞存活和/或功能恢复至关重要。
