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mRNA Redistribution during Permanent Focal Cerebral Ischemia

机译:永久性局灶性脑缺血期间mRNA的重新分布

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Translation arrest occurs in neurons following focal cerebral ischemia and is irreversible in penumbral neurons destined to die. Following global cerebral ischemia, mRNA is sequestered away from 40S ribosomal subunits as mRNA granules, precluding translation. Here, we investigated mRNA granule formation using fluorescence in situ histochemistry out to 8 h permanent focal cerebral ischemia using middle cerebral artery occlusion in Long Evans rats with and without diabetes. Neuronal mRNA granules colocalized with PABP, HuR, and NeuN, but not 40S or 60S ribosomal subunits, or organelle markers. The volume of brain with mRNA granule-containing neurons decreased exponentially with ischemia duration, and was zero after 8 h permanent focal cerebral ischemia or any duration of ischemia in diabetic rats. These results show that neuronal mRNA granule response has a limited range of insult intensity over which it is expressed. Identifying the limits of effective neuronal stress response to ischemia will be important for developing effective stroke therapies.
机译:翻译停滞发生在局灶性脑缺血后的神经元中,并且在注定要死亡的半影神经元中是不可逆的。全局脑缺血后,mRNA被隔离为40S核糖体亚基的mRNA颗粒,从而阻止了翻译。在这里,我们使用Long Evans大鼠在患有和不患有糖尿病的Long Evans大鼠中使用荧光原位组织化学研究了8h永久性局灶性脑缺血的mRNA颗粒形成。神经元mRNA颗粒与PABP,HuR和NeuN共定位,但不与40S或60S核糖体亚基或细胞器标记共定位。在糖尿病大鼠中,永久性局灶性脑缺血或任何缺血持续时间8小时后,具有mRNA颗粒的神经元的大脑体积随缺血持续时间呈指数下降,并且为零。这些结果表明,神经元mRNA颗粒反应在其表达范围内具有有限的侮辱强度范围。识别对缺血的有效神经元应激反应的局限性对于开发有效的中风疗法很重要。

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