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

• 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.

Nyckelord

Animals

Animals

Newborn

Blotting

Western/methods

Brain Ischemia/genetics/metabolism/*prevention & control

Cell Count/methods

Female

Functional Laterality/physiology

Immunohistochemistry/methods

Male

Mice

Mice

Knockout

Mortality

NAD/metabolism

Poly(ADP-ribose) Polymerases/*deficiency/genetics/metabolism

Rabbits

Sex Factors

Time Factors

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)