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

Henrik Hagberg, Mary Ann Ann Wilson, Hiroko Matsushita, Changlian Zhu, Mary Lange, Malin Gustavsson, Marc F. Poitras, Ted M Dawson, Valina 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

Fingerprint

Brain Injuries
Brain
Ischemia
Genes
Poly(ADP-ribose) Polymerases
NAD
Poly Adenosine Diphosphate Ribose
Animals
Western Blotting
Rats
Poly (ADP-Ribose) Polymerase-1
Hypoxia
Experiments

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

PARP-1 gene disruption in mice preferentially protects males from perinatal brain injury. / Hagberg, Henrik; Wilson, Mary Ann Ann; Matsushita, Hiroko; Zhu, Changlian; Lange, Mary; Gustavsson, Malin; Poitras, Marc F.; Dawson, Ted M; Dawson, Valina; Northington, Frances; Johnston, Michael V.

In: Journal of Neurochemistry, Vol. 90, No. 5, 09.2004, p. 1068-1075.

Research output: Contribution to journalArticle

Hagberg, Henrik ; Wilson, Mary Ann Ann ; Matsushita, Hiroko ; Zhu, Changlian ; Lange, Mary ; Gustavsson, Malin ; Poitras, Marc F. ; Dawson, Ted M ; Dawson, Valina ; Northington, Frances ; Johnston, Michael V. / PARP-1 gene disruption in mice preferentially protects males from perinatal brain injury. In: Journal of Neurochemistry. 2004 ; Vol. 90, No. 5. pp. 1068-1075.
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