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未成熟大鼠海马体发育过程中及癫痫持续状态后微管相关蛋白2(MAP2)表达的变化

Changes in microtubule-associated protein-2 (MAP2) expression during development and after status epilepticus in the immature rat hippocampus.

作者信息

Jalava Niina S, Lopez-Picon Francisco R, Kukko-Lukjanov Tiina-Kaisa, Holopainen Irma E

机构信息

Department of Pharmacology, Drug Development, and Therapeutics, Institute of Biomedicine, University of Turku, Itäinen Pitkäkatu 4B, FIN-20014 Turku, Finland.

出版信息

Int J Dev Neurosci. 2007 Apr;25(2):121-31. doi: 10.1016/j.ijdevneu.2006.12.001. Epub 2006 Dec 20.

DOI:10.1016/j.ijdevneu.2006.12.001
PMID:17229541
Abstract

In this study, we analyzed the spatiotemporal expression patterns of the high-molecular weight (MAP2a and b) and low-molecular weight (MAP2c and d) cytoskeletal microtubule-associated protein-2 (MAP2) isoforms with Western blotting, and the cellular localization of the high-molecular weight MAP2 isoforms with immunocytochemistry in the hippocampi of 1- to 21-day-old rats. Moreover, the temporal profile (from 30 min to 1 week) of MAP2 isoform reactivity to kainic acid-induced status epilepticus was studied in P9 rats. During development, the expression of the high-molecular weight MAP2 isoforms significantly increased, while the low-molecular weight isoforms decreased, the most prominent changes occurring during the second postnatal week. This developmental increase in the high-molecular weight MAP2 expression was also confirmed with immunocytochemistry, which showed increased immunoreactivity, particularly in the molecular layers of the dentate gyrus, and in CA1 and CA3 stratum radiatum. In 9-day-old rats, status epilepticus resulted in a rapid transient increase (about 210%) in the high-molecular weight MAP2 expression, without any effect on the low-molecular weight MAP2. Moreover, disturbed dendritic structure in the CA1 and CA3 stratum radiatum was manifested as formation of varicosities 3h after the kainic acid treatment. The strictly developmentally regulated MAP2 isoform expression suggests different functional roles for these proteins during the postnatal development in the rat hippocampus. Moreover, high-molecular weight MAP2s may play a role in nerve cell survival during cell stress.

摘要

在本研究中,我们用蛋白质免疫印迹法分析了高分子量(MAP2a和b)和低分子量(MAP2c和d)细胞骨架微管相关蛋白2(MAP2)亚型的时空表达模式,并通过免疫细胞化学法研究了1至21日龄大鼠海马中高分子量MAP2亚型的细胞定位。此外,还研究了P9大鼠中MAP2亚型对 kainic 酸诱导的癫痫持续状态的反应的时间变化情况(从30分钟到1周)。在发育过程中,高分子量MAP2亚型的表达显著增加,而低分子量亚型的表达则下降,最显著的变化发生在出生后的第二周。免疫细胞化学也证实了高分子量MAP2表达的这种发育性增加,其显示免疫反应性增强,特别是在齿状回的分子层以及CA1和CA3辐射层中。在9日龄大鼠中,癫痫持续状态导致高分子量MAP2表达迅速短暂增加(约210%),而对低分子量MAP2没有任何影响。此外,在 kainic 酸处理后3小时,CA1和CA3辐射层中树突结构紊乱表现为静脉曲张的形成。严格受发育调控的MAP2亚型表达表明这些蛋白质在大鼠海马出生后发育过程中具有不同的功能作用。此外,高分子量MAP2可能在细胞应激期间的神经细胞存活中发挥作用。

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