PARP-1 gene disruption in mice preferentially protects males from perinatal brain injury

被引:237
作者
Hagberg, H
Wilson, MA
Matsushita, H
Zhu, CL
Lange, M
Gustavsson, M
Poitras, MF
Dawson, TM
Dawson, VL
Northington, F
Johnston, MV
机构
[1] Sahlgrenska Univ Hosp, Perinatal Ctr, Gothenburg, Sweden
[2] Johns Hopkins Sch Med, Kennedy Krieger Res Inst, Baltimore, MD USA
[3] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA
[4] Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA
[5] Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD USA
关键词
brain injury; hypoxia; ischemia; neonatal; poly(ADP-ribose)polymerase;
D O I
10.1111/j.1471-4159.2004.02547.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
Poly(ADP-ribose) polymerase-1 is over-activated in the adult brain in response to ischemia and contributes to neuronal death, but its role in perinatal brain injury remains uncertain. To address this issue, 7-day-old wild-type (wt) and PARP-1 gene deficient (parp+/- and parp-/-) Sv129/CD-1 hybrid mice were subjected to unilateral hypoxia-ischemia and histologic damage was assessed 10 days later by two evaluators. Poly(ADP-ribose) polymerase-1 knockout produced moderate but significant (p<0.05) protection in the total group of animals, but analysis by sex revealed that males were strongly protected (p<0.05) in contrast to females in which there was no significant effect. Separate experiments demonstrated that PARP-1 was activated over 1-24 h in both females and males after the insult in neonatal wt mice and rats using immnocytochemistry and western blotting for poly(ADP-ribose). Brain levels of NAD(+) were also significantly reduced, but the decrease of NAD(+) during the early post-hypoxia-ischemia (HI) phase was only seen in males. The results indicate that hypoxia-ischemia activates Poly(ADP-ribose) polymerase-1 in the neonatal brain and that the sex of the animal strongly influences its role in the pathogenesis of brain injury.
引用
收藏
页码:1068 / 1075
页数:8
相关论文
共 44 条
  • [21] Estrogen as a neuroprotectant in stroke
    Hurn, PD
    Macrae, IM
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2000, 20 (04) : 631 - 652
  • [22] SEXUAL DIMORPHISM IN THE DEVELOPMENTAL REGULATION OF BRAIN AROMATASE
    HUTCHISON, JB
    BEYER, C
    HUTCHISON, RE
    WOZNIAK, A
    [J]. JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1995, 53 (1-6) : 307 - 313
  • [23] Jacobson EL, 1997, METHOD ENZYMOL, V280, P221
  • [24] MONOCLONAL-ANTIBODIES TO POLY(ADENOSINE DIPHOSPHATE RIBOSE) RECOGNIZE DIFFERENT STRUCTURES
    KAWAMITSU, H
    HOSHINO, H
    OKADA, H
    MIWA, M
    MOMOI, H
    SUGIMURA, T
    [J]. BIOCHEMISTRY, 1984, 23 (16) : 3771 - 3777
  • [25] Apoptosis detection in brain using low-magnification dark-field microscopy
    Lange, MS
    Johnston, MV
    Tseng, EE
    Baumgartner, WA
    Blue, ME
    [J]. EXPERIMENTAL NEUROLOGY, 1999, 158 (01) : 254 - 260
  • [26] Le Rhun Y, 1998, BIOCHEM BIOPH RES CO, V245, P1
  • [27] Mandir AS, 2000, J NEUROSCI, V20, P8005
  • [28] PHYSIOLOGICAL AND PATHOPHYSIOLOGICAL ROLES OF EXCITATORY AMINO-ACIDS DURING CENTRAL-NERVOUS-SYSTEM DEVELOPMENT
    MCDONALD, JW
    JOHNSTON, MV
    [J]. BRAIN RESEARCH REVIEWS, 1990, 15 (01) : 41 - 70
  • [29] Activation of poly(ADP-Ribose) polymerase in the rat hippocampus may contribute to cellular recovery following sublethal transient global ischemia
    Nagayama, T
    Simon, RP
    Chen, DX
    Henshall, DC
    Pei, W
    Stetler, RA
    Chen, J
    [J]. JOURNAL OF NEUROCHEMISTRY, 2000, 74 (04) : 1636 - 1645
  • [30] Nakajima W, 2000, J NEUROSCI, V20, P7994