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首页> 外文期刊>The European Journal of Neuroscience >Specific pathophysiological functions of JNK isoforms in the brain.
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Specific pathophysiological functions of JNK isoforms in the brain.

机译:JNK同工型在脑中的特定病理生理功能。

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We have investigated the effect of JNK1 ko, JNK2 ko, JNK3 ko, JNK2+3 ko and c-JunAA mutation on neuronal survival in adult transgenic mice following ischemia, 6-hydroxydopamine induced neurotoxicity, axon transection and kainic acid induced excitotoxicity. Deletion of JNK isoforms indicated the compartment-specific expression of JNK isoforms with 46-kDa JNK1 as the main phosphorylated JNK isoform. Permanent occlusion of the MCA significantly enlarged the infarct area in JNK1 ko, which showed an increased expression of JNK3 in the penumbra. Survival of dopaminergic neurons in the substantia nigra compacta (SNC) following intrastriatal injection of 6-hydroxydopamine was transiently improved in JNK3 ko and c-JunAA mice after 7 days, but not 60 days. Following transection of the medial forebrain bundle, however, JNK3 ko conferred persisting neuroprotection of axotomised SNC neurons. None of the JNK ko and c-JunAA mutation affected the survival of facial motoneurons following peripheral axotomy when investigated after 90 days. Finally, we determined the impact of JNK ko on the survival of animals and the degeneration of hippocampal neurons following kainic acid. JNK3 ko mice were substantially resistant against and survived kainic acid-induced seizures. JNK3 ko and JNK1 ko showed a nonsignificant tendency for decreased or increased death of hippocampal neurons, respectively. Surprisingly, the deletion of a single JNK isoform did not attenuate the immunocytochemical signal of phosphorylated c-Jun irrespective on the experimental set-up. This comprehensive study provides novel insights into the context-dependent physiological and pathological functions of JNK isoforms.
机译:我们已经研究了JNK1 ko,JNK2 ko,JNK3 ko,JNK2 + 3 ko和c-JunAA突变对成年转基因小鼠局部缺血,6-羟基多巴胺诱导的神经毒性,轴突横断和海藻酸诱导的兴奋性毒性的神经元存活的影响。 JNK同工型的删除表明JNK同工型的特定于车厢的特定表达,其中46-kDa JNK1是主要的磷酸化JNK同工型。 MCA的永久性阻塞显着扩大了JNK1 ko中的梗塞区域,这表明JNK3在半影中的表达增加了。在JNK3 ko和c-JunAA小鼠中,纹状体内注射6-羟基多巴胺后,多巴胺能神经元的存活在7天后短暂改善,但不是60天。然而,在横断内侧前脑束之后,JNK3 ko赋予了轴突化的SNC神经元持续的神经保护。 90天后调查发现,JNK ko和c-JunAA突变均未影响外周轴突切开术后面部运动神经元的存活。最后,我们确定了JNK ko对海藻酸后动物存活和海马神经元变性的影响。 JNK3 ko小鼠对海藻酸诱导的癫痫病具有实质上的抵抗力,并能存活下来。 JNK3 ko和JNK1 ko分别显示出减少或增加海马神经元死亡的趋势。出乎意料的是,无论实验设置如何,单个JNK同工型的缺失都不会减弱磷酸化c-Jun的免疫细胞化学信号。这项全面的研究为JNK同工型的上下文相关的生理和病理功能提供了新颖的见解。

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