Different apoptotic mechanisms are activated in male and female brains after neonatal hypoxia-ischaemia

被引:221
作者
Zhu, CL
Xu, FL
Wang, XY
Shibata, M
Uchiyama, Y
Blomgren, K
Hagberg, H
机构
[1] Univ Gothenburg, Arvid Carlsson Inst Neurosci, Inst Clin Neurosci, SE-40530 Gothenburg, Sweden
[2] Zhengzhou Univ, Dept Pediat, Affiliated Hosp 3, Zhengzhou, Peoples R China
[3] Univ Gothenburg, Dept Physiol, Perinatal Ctr, SE-40530 Gothenburg, Sweden
[4] Osaka Univ, Dept Cell Biol & Neurosci, Grad Sch Med, Osaka, Japan
[5] Queen Silvia Childrens Hosp, Dept Pediat, Gothenburg, Sweden
[6] Univ Gothenburg, Dept Obstet & Gynecol, Sahlgrenska Hosp, Gothenburg, Sweden
关键词
apoptosis-inducing factor; brain development; caspase; cell death; hypoxia-ischaemia; sex;
D O I
10.1111/j.1471-4159.2005.03639.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1016 / 1027
页数:12
相关论文
共 55 条
  • [1] Gender-linked brain injury in experimental stroke
    Alkayed, NJ
    Harukuni, I
    Kimes, AS
    London, ED
    Traystman, RJ
    Hurn, PD
    [J]. STROKE, 1998, 29 (01) : 159 - 165
  • [2] SEX-DIFFERENCES IN DENDRITIC STRUCTURE IN THE PREOPTIC AREA OF THE JUVENILE MACAQUE MONKEY BRAIN
    AYOUB, DM
    GREENOUGH, WT
    JURASKA, JM
    [J]. SCIENCE, 1983, 219 (4581) : 197 - 198
  • [3] Brain sexual differentiation and gonadotropins secretion in the rat
    Becú-Villalobos, D
    Iglesias, AG
    Díaz-Torga, G
    Hockl, P
    Libertun, C
    [J]. CELLULAR AND MOLECULAR NEUROBIOLOGY, 1997, 17 (06) : 699 - 715
  • [4] Synergistic activation of caspase-3 by m-calpain after neonatal hypoxia-ischemia - A mechanism of "pathological apoptosis"?
    Blomgren, K
    Zhu, CL
    Wang, XY
    Karlsson, JO
    Leverin, AL
    Bahr, BA
    Mallard, C
    Hagberg, H
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (13) : 10191 - 10198
  • [5] Protective effects of moderate hypothermia after neonatal hypoxia-ischemia:: Short- and long-term outcome
    Bona, E
    Hagberg, H
    Loberg, EM
    Bågenholm, R
    Thoresen, M
    [J]. PEDIATRIC RESEARCH, 1998, 43 (06) : 738 - 745
  • [6] The autophagosomal-lysosomal compartment in programmed cell death
    Bursch, W
    [J]. CELL DEATH AND DIFFERENTIATION, 2001, 8 (06) : 569 - 581
  • [7] Medial preoptic and anterior hypothalamic regions of the rhesus monkey: cytoarchitectonic comparison with the human and evidence for sexual dimorphism
    Byne, W
    [J]. BRAIN RESEARCH, 1998, 793 (1-2) : 346 - 350
  • [8] Sex chromosome genes directly affect brain sexual differentiation
    Carruth, LL
    Reisert, I
    Arnold, AP
    [J]. NATURE NEUROSCIENCE, 2002, 5 (10) : 933 - 934
  • [9] Caspase inhibitor affords neuroprotection with delayed administration in a rat model of neonatal hypoxic-ischemic brain injury
    Cheng, Y
    Deshmukh, M
    D'Costa, A
    Demaro, JA
    Gidday, JM
    Shah, A
    Sun, YL
    Jacquin, MF
    Johnson, EM
    Holtzman, DM
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (09) : 1992 - 1999
  • [10] Gender differences in learning and memory after pediatric traumatic brain injury
    Donders, J
    Hoffman, NA
    [J]. NEUROPSYCHOLOGY, 2002, 16 (04) : 491 - 499