Different apoptotic mechanisms are activated in male and female brains after neonatal hypoxia-ischaemia
Different apoptotic mechanisms are activated in male and female brains after neonatal hypoxia-ischaemia
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DOI：
10.1111/j.1471-4159.2005.03639.x
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发表时间：
2006-02-01
影响因子：
4.7
通讯作者：
Hagberg, H
中科院分区：
文献类型：
--
作者：
Zhu, CL;Xu, FL;Hagberg, H
在出生后第5、9、21或60天（P）的C57/BL 6小鼠中，在单侧缺氧缺血（HI）后评价了与性别相关的脑损伤，对应于发育中的早产儿、足月儿、青少年和成年人的脑。有没有性别差异，脑损伤时，严重的侮辱，病理评分或组织损失的评价，但当侮辱是中度，成年（P60）女性表现出较少的损伤。在未成熟（P9）的男性大脑中，神经元表现出更明显的易位的凋亡诱导因子（AIF）（AIF从线粒体部分的损失和核AIF增加）后HI，而女性脑神经元表现出更强的激活caspase 3（更明显的损失的caspase 3原，增加裂解caspase 3和caspase 3酶活性增加）。另外两种损伤机制，过氧亚硝酸盐诱导的硝基酪氨酸形成和自噬，在P9时雄性和雌性之间没有差异。这些数据表明，成年雌性小鼠的CNS对HI的抵抗力高于雄性小鼠，而新生小鼠的损伤程度无性别差异。然而，关键的性别依赖性差异在体内表现出关于细胞，骨化相关机制。
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.