Bertrand N, Sirén A L, Tworek D, McCarron R M, Spatz M
Laboratoire de Pharmacodynamie, Faculté de Pharmacie, Dijon, France.
J Cereb Blood Flow Metab. 2000 Jul;20(7):1056-65. doi: 10.1097/00004647-200007000-00005.
This study presents a quantitative comparison of the time courses and regional distribution of both constitutive HSC73 and inducible HSP72 mRNA expression and their respective encoded proteins between young (3-week-old) and adult (3-month-old) gerbil hippocampus after transient global ischemia. The constitutive expression of HSC73 mRNA and protein in the hippocampus of the young sham-operated gerbils was significantly higher than in the adults. The HSC73 mRNA expression after ischemia in the CA1 layer of young gerbils was greater than in adult gerbils. HSC73 immunoreactivity was not significantly changed after ischemia-reperfusion in adult hippocampus, whereas it decreased in young gerbils. Ischemia-reperfusion led to induction of HSP72 mRNA expression throughout the hippocampus of both young and adult gerbils. HSP72 mRNA induction was more intense and sustained in the CA1 subfield of young gerbils; this was associated with a marked induction of HSP72 proteins and neuronal survival. The transient expression of HSP72 mRNA in the CA1 layer of adult gerbils was not associated with a subsequent synthesis of HSP72 protein but was linked to neuronal loss. Expression of HSP72 mRNA was shifted to an earlier period of reflow in CA3 and dentate gyrus (DG) subfields of young animals. These findings suggest that the induction of both HSP72 mRNA and proteins in the CA1 pyramidal neurons of young gerbils, as well as the higher constitutive expression of HSC73, may partially contribute to higher neuronal resistance of young animals to transient cerebral ischemia.
本研究对短暂性全脑缺血后幼年(3周龄)和成年(3月龄)沙鼠海马中组成型HSC73和诱导型HSP72 mRNA表达及其各自编码蛋白的时间进程和区域分布进行了定量比较。在未手术的幼年沙鼠海马中,HSC73 mRNA和蛋白的组成型表达显著高于成年沙鼠。幼年沙鼠缺血后CA1层的HSC73 mRNA表达高于成年沙鼠。成年海马缺血再灌注后HSC73免疫反应性无显著变化,而幼年沙鼠则降低。缺血再灌注导致幼年和成年沙鼠整个海马中HSP72 mRNA表达的诱导。幼年沙鼠CA1亚区的HSP72 mRNA诱导更强且持续时间更长;这与HSP72蛋白的显著诱导和神经元存活有关。成年沙鼠CA1层中HSP72 mRNA的短暂表达与随后的HSP72蛋白合成无关,但与神经元丢失有关。幼年动物CA3和齿状回(DG)亚区中HSP72 mRNA的表达转移到再灌注的早期阶段。这些发现表明,幼年沙鼠CA1锥体神经元中HSP72 mRNA和蛋白的诱导,以及HSC73较高的组成型表达,可能部分有助于幼年动物对短暂性脑缺血具有更高的神经元抵抗力。