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

Henrik Hagberg, Mary Ann Wilson, Hiroko Matsushita, Changlian Zhu, Mary Lange, Malin Gustavsson, Marc F. Poitras, Ted M. Dawson, Valina L. Dawson, Frances Northington, Michael V. Johnston

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1068-1075
Number of pages8
JournalJournal of Neurochemistry
Volume90
Issue number5
DOIs
StatePublished - Sep 2004

Keywords

  • Brain injury
  • Hypoxia
  • Ischemia
  • Neonatal
  • Poly(ADP-ribose)polymerase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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