CORRELATION BETWEEN SEIZURE INTENSITY AND STRESS PROTEIN EXPRESSION AFTER LIMBIC EPILEPSY IN THE RAT-BRAIN
CORRELATION BETWEEN SEIZURE INTENSITY AND STRESS PROTEIN EXPRESSION AFTER LIMBIC EPILEPSY IN THE RAT-BRAIN
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DOI：
10.1016/0306-4522(95)92049-p
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发表时间：
1995-03-01
期刊：
影响因子：
3.3
通讯作者：
KIESSLING, M
中科院分区：
文献类型：
--
作者：
GASS, P;PRIOR, P;KIESSLING, M
诱导热休克/应激蛋白是一种被称为“应激反应”的普遍细胞防御机制的关键特征。本研究调查了热休克蛋白的表达是否与日益强烈的癫痫发作活动所致神经元损伤的程度相关。给成年SD大鼠腹腔注射8、10、12 mg/kg的海人酸致边缘癫痫，其发作强度和发作持续时间与剂量密切相关。应用免疫细胞化学和免疫印迹方法，分别针对热休克蛋白72、热休克蛋白90和治愈休克蛋白27这三大类应激蛋白的代表成员，对显微解剖的脑区进行应激蛋白表达的研究。热休克蛋白72在对照组动物脑中不表达，但在边缘系统、皮质、纹状体和丘脑的神经元中明显表达，高峰出现在2 4h，随着癫痫发作强度的增加，热休克蛋白72的水平逐渐升高，其序列反映了海人酸易感的海马亚群的等级顺序。与热休克蛋白72相反，热休克蛋白90在未经处理的对照组动物的所有脑区以及在边缘癫痫发作后的任何时间点都显著表达且同样丰富。在未经治疗的动物和癫痫发作后的动物的大脑中都没有检测到热休克蛋白27。目前的研究表明，热休克蛋白72在特定神经元亚群中的诱导阈值与癫痫发作的强度和持续时间明显相关。此外，我们的实验还定义了热休克蛋白72表达的一个狭窄范围，超过这个上限，热休克蛋白72的合成急剧下降。这些发现反映了海马神经元经历边缘癫痫诱导的神经元变性的风险。热休克蛋白72的表达是否只是可逆性神经元损伤的有价值的标记物，或者实际上具有神经保护作用，仍有待确定。
Induction of heat shock/stress proteins is a key feature of a universal mechanism of cellular defence to injury known as the ''stress response''. The present study investigated whether heat shock protein expression correlates with the extent of neuronal injury inflicted by increasingly intense seizure activity. Limbic epilepsy was elicited by injecting intraperitoneally 8, 10 or 12 mg/kg kainic acid in adult Sprague-Dawley rats, resulting in graded degrees of seizure intensity and duration that closely correlated with the respective dose. Stress protein expression was investigated by immunocytochemistry and western blot analysis of microdissected brain areas with specific antibodies directed against representative members of three major classes of stress proteins, i.e. heat shock protein 72, heat shock protein 90 and heal shock protein 27, respectively. Heat shock protein 72 was absent in the brains of control animals, but markedly induced after limbic seizures in neurons of the limbic system, cortex, striatum and thalamus, with peak levels at 24 h. An increasing degree of seizure intensity caused a graded increase of heat shack protein 72 levels with a sequence reflecting the rank order of kainic acid susceptible hippocampal subpopulations. In contrast to heat shock protein 72, heat shock protein 90 was markedly expressed and equally abundant in all brain areas of untreated control animals and at any time point investigated following limbic seizures. Heat shock protein 27 was not detected in the brain of untreated animals nor following epilepsy. The present investigations demonstrate that the induction threshold of heat shock protein 72 in specific neuronal subpopulations clearly correlates with seizure intensity and duration. In addition, our experiments also define a narrow range of heat shock protein 72 expression with an upper limit beyond which heat shock protein 72 synthesis sharply declines.These findings reflect the risk of hippocampal neurons to undergo limbic seizure induced neuronal degeneration. It remains to be determined whether heat shock protein 72 expression is only a valuable marker for reversible neuronal injury or actually confers a neuroprotective effect.