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点燃癫痫发作诱导的大鼠海马中蛋白激酶C同工酶(α-ζ)基因表达的同工酶特异性变化。

Isozyme specific changes in the expression of protein kinase C isozyme (alpha-zeta) genes in the hippocampus of rats induced by kindling epileptogenesis.

作者信息

Kamphuis W, Hendriksen E, Lopes da Silva F H

机构信息

Institute of Neurobiology, University of Amsterdam, Netherlands.

出版信息

Brain Res. 1995 Dec 8;702(1-2):94-100. doi: 10.1016/0006-8993(95)01011-0.

Abstract

The transcript levels of the protein kinase C (PKC) isoform genes during the development of a kindled epileptogenic focus, elicited by stimulation of Schaffer collateral/commissural fibres in the CA1 area of the rat hippocampus, were compared with the expression levels in control animals using a semi-quantitative in situ hybridization approach. In the hippocampus of control animals, the levels of PKC-alpha-zeta transcripts showed a gene-specific expression pattern and significant differences in expression level were observed between the neurons of CA1, CA3 and fascia dentata. In the early stages of kindling epileptogenesis, i.e. following 6 and 14 afterdischarges, specific changes in the expression levels of PKC-beta, -epsilon, and -zeta but not of PKC-alpha, -gamma, and -delta were found. PKC-beta expression was decreased in CA1, while the PKC-epsilon and -zeta specific hybridization signals were increased in CA1, CA3 and fascia dentata. In fully kindled animals, that had experienced 10 generalized seizures, most expression levels tended to return to control values. One month after the last seizure no significant alterations were encountered. These results indicate an involvement of specific PKC-isoform gene expression in the induction of an epileptogenic focus, but not in the maintenance of the long-lasting kindled state.

摘要

通过刺激大鼠海马体CA1区的Schaffer侧支/联合纤维引发点燃性致痫灶形成过程中,采用半定量原位杂交方法,比较蛋白激酶C(PKC)亚型基因的转录水平与对照动物中的表达水平。在对照动物的海马体中,PKC-α-ζ转录本水平呈现基因特异性表达模式,并且在CA1、CA3和齿状回的神经元之间观察到表达水平的显著差异。在点燃性癫痫发生的早期阶段,即在6次和14次放电后,发现PKC-β、-ε和-ζ的表达水平有特异性变化,但PKC-α、-γ和-δ没有。PKC-β在CA1中的表达降低,而PKC-ε和-ζ的特异性杂交信号在CA1、CA3和齿状回中增加。在经历了10次全身性癫痫发作的完全点燃动物中,大多数表达水平趋于恢复到对照值。最后一次癫痫发作后一个月未发现明显改变。这些结果表明特定PKC亚型基因表达参与致痫灶的诱导,但不参与长期点燃状态的维持。

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