Zhu Changlian, Xu Falin, Wang Xiaoyang, Shibata Masahiro, Uchiyama Yasuo, Blomgren Klas, Hagberg Henrik
Arvid Carlsson Institute of Neuroscience at the Institute of Clinical Neuroscience, Göteborg University, Göteborg, Sweden.
J Neurochem. 2006 Feb;96(4):1016-27. doi: 10.1111/j.1471-4159.2005.03639.x. Epub 2006 Jan 12.
Sex-related brain injury was evaluated after unilateral hypoxia-ischaemia (HI) in C57/BL6 mice on postnatal day (P) 5, 9, 21 or 60, corresponding developmentally to premature, term, juvenile and adult human brains. There was no sex difference in brain injury when the insult was severe, as evaluated by pathological scoring or tissue loss, but when the insult was moderate, adult (P60) females displayed less injury. In the immature (P9) male brains, neurones displayed a more pronounced translocation of apoptosis-inducing factor (AIF) (loss of AIF from the mitochondrial fraction and increase in nuclear AIF) after HI, whereas the female brain neurones displayed a stronger activation of caspase 3 (more pronounced loss of pro-caspase 3, increase in cleaved caspase 3 and increase in caspase 3 enzymatic activity). Two other mechanisms of injury, peroxynitrite-induced formation of nitrotyrosine and autophagy, were no different between males and females at P9. These data show that the CNS is more resistant to HI in adult females compared with males, whereas no sex differences were found in the extent of injury in neonatal mice. However, critical sex-dependent differences were demonstrated in vivo with regard to cellular, apoptosis-related mechanisms.
在出生后第5天、第9天、第21天或第60天的C57/BL6小鼠中，对单侧缺氧缺血（HI）后的性别相关脑损伤进行了评估，这在发育上分别对应于早产、足月、幼年和成年人类大脑。通过病理评分或组织损失评估，当损伤严重时，脑损伤不存在性别差异，但当损伤为中度时，成年（P60）雌性小鼠的损伤较轻。在未成熟（P9）雄性小鼠大脑中，HI后神经元显示出凋亡诱导因子（AIF）更明显的易位（线粒体部分AIF丢失，细胞核AIF增加），而雌性小鼠大脑神经元显示出半胱天冬酶3更强的激活（前半胱天冬酶3更明显的丢失、裂解的半胱天冬酶3增加以及半胱天冬酶3酶活性增加）。在P9时，另外两种损伤机制，即过氧亚硝酸盐诱导的硝基酪氨酸形成和自噬，在雄性和雌性之间没有差异。这些数据表明，与雄性相比，成年雌性中枢神经系统对HI的耐受性更强，而新生小鼠在损伤程度上未发现性别差异。然而，在体内关于细胞凋亡相关机制方面，显示出了关键的性别依赖性差异。
