DNA fragmentation and immediate early gene expression in rat striatum following quinolinic acid administration.
DNA fragmentation and immediate early gene expression in rat striatum following quinolinic acid administration.
复制标题
喹啉酸给药后大鼠纹状体中的 DNA 碎片和立即早期基因表达。
DOI：
10.1006/exnr.1995.1023
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Young,AB
中科院分区：
文献类型：
--
作者：
Dure4th,LS;Wiess,S;Standaert,DG;Rudolf,G;Testa,CM;Young,AB
兴奋性毒性细胞死亡被假设为导致许多神经病理学病症，包括缺氧/缺血性脑病、低血糖症、帕金森病和亨廷顿病。兴奋性毒性损伤引起的神经元死亡是一个活跃的过程，伴随着即刻早期基因转录的激活，导致基因表达的继发性变化。神经毒性细胞死亡的另一个特征是DNA片段化，这可能表明细胞核即将解体。已经描述了一种用于原位标记片段化DNA的技术，其允许精确确定兴奋性毒性损伤后神经元的解剖和时间分布。为了研究这一现象，我们进行了原位缺口平移脑组织大鼠进行了立体定位放置纹状体内注射喹啉酸。此外，在这些相同的动物中，我们分析了c-fos mRNA的表达，以比较兴奋性毒性损伤后即刻早期基因激活的DNA片段化的时间过程和区域分布。我们的分析表明，c-fos的表达增加后不久喹啉酸注射，是广泛存在于大鼠脑，但有效地缺席注射后24小时。然而，DNA片段化仅限于纹状体，并且在注射后24小时达到最大。这些结果表明原位缺口平移检测区域神经病理学的敏感性和c-fos表达的时间和空间的关系，兴奋性神经元死亡。
Excitotoxic cell death is hypothesized to contribute to numerous neuropathologic conditions, including hypoxic/ischemic encephalopathy, hypoglycemia, Parkinson's disease, and Huntington's disease. Neuronal death from excitotoxic lesions has been shown to be an active process, with activation of immediate early gene transcription, resulting in secondary changes in gene expression. Another feature of neurotoxic cell death that has been examined is the presence of DNA fragmentation, which presumably indicates impending nuclear disintegration. A technique has been described for labeling fragmented DNA in situ, allowing precise determination of the anatomic and temporal distribution of neurons after an excitotoxic lesion. To investigate this phenomenon, we performed in situ nick translation on brain tissue from rats that have undergone stereotaxically placed intrastriatal quinolinic acid injections. Furthermore, in these same animals we analyzed the expression of c-fos mRNA to compare the time course and regional distribution of DNA fragmentation with immediate early gene activation after an excitotoxic lesion. Our analysis indicates that c-fos expression increases soon after quinolinic acid injection, is widespread in rat brain, but is effectively absent by 24 h postinjection. DNA fragmentation, however, is limited to striatum and is maximal at 24 h after injection. These results demonstrate the sensitivity of in situ nick translation for the detection of regional neuropathology and illustrate the temporal and spatial relationship of c-fos expression to excitotoxic neuronal death.