title: Different apoptotic mechanisms are activated in male and female brains after neonatal hypoxia-ischaemia.
abstract: 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.
authors.affiliation: Arvid Carlsson Institute of Neuroscience at the Institute of Clinical Neuroscience, Göteborg University, Göteborg, Sweden. changlian.zhu@neuro.gu.se
authors.forename: Changlian
authors.initials: C
authors.lastname: Zhu
authors.forename: Falin
authors.initials: F
authors.lastname: Xu
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
authors.forename: Masahiro
authors.initials: M
authors.lastname: Shibata
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Klas
authors.initials: K
authors.lastname: Blomgren
authors.forename: Henrik
authors.initials: H
authors.lastname: Hagberg
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D001921:Brain / Q000473:pathology / Q000503:physiopathology*; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D002452:Cell Count; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012727:Sex Characteristics
chemical_list: C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases