Delivery is a risky event for the newborn. The mother-dependent respiration has to be replaced by an autonomous pulmonary breathing immediately after delivery. If delayed, hypoxia is sustained, leading inevitably to cell death, even after resuscitation. Re-oxygenation triggers a metabolic cascade worsening and/or delaying the recovery of the newborn. With an experimental model in rat, we observed that perinatal asphyxia (PA) leads to neuronal death and neurite atrophy in basal ganglia, and hippocampus, with behavioural deficits reflecting the severity of the insult. Cell death is observed even 30 days after birth with apoptotic features. Pro (BAD)- and anti (BCL-2, ERK-2)- apoptotic, as well as neurogenesis and neuritogenesis (BDNF, bFGF) promoting proteins are concomitantly increased. Nicotinamide can prevent some of the effects produced by PA, suggesting the involvement of the sentinel protein poly(ADP-ribose) polymerase-1 (PARP-1), known to be overactivated whenever there is a menace to the genome. We report here on the effect of PA on PARP-1 mRNA levels using Real Time PCR, as well as on PARP-1 activity in the nuclear fraction of brain, and heart tissue, using a colorimetric method. It was found that the expression and activity of PARP-1 was increased in brain tissue following PA. In heart, PARP-1activity was first increased 8 h, but then decreased 24 h after delivery in PA, as compared to control pups. In summary, the present results support the idea that PARP-1 overactivation is an underlying factor of the long term effects produced by PA, and that PARP-1 inhibition provides neuroprotection.
Acute and long-term neuronal loss induced by perinatal asphyxia: activation of pro-apoptotic, anti-apoptotic and sentinel proteins
2009-01-01
Abstract
Delivery is a risky event for the newborn. The mother-dependent respiration has to be replaced by an autonomous pulmonary breathing immediately after delivery. If delayed, hypoxia is sustained, leading inevitably to cell death, even after resuscitation. Re-oxygenation triggers a metabolic cascade worsening and/or delaying the recovery of the newborn. With an experimental model in rat, we observed that perinatal asphyxia (PA) leads to neuronal death and neurite atrophy in basal ganglia, and hippocampus, with behavioural deficits reflecting the severity of the insult. Cell death is observed even 30 days after birth with apoptotic features. Pro (BAD)- and anti (BCL-2, ERK-2)- apoptotic, as well as neurogenesis and neuritogenesis (BDNF, bFGF) promoting proteins are concomitantly increased. Nicotinamide can prevent some of the effects produced by PA, suggesting the involvement of the sentinel protein poly(ADP-ribose) polymerase-1 (PARP-1), known to be overactivated whenever there is a menace to the genome. We report here on the effect of PA on PARP-1 mRNA levels using Real Time PCR, as well as on PARP-1 activity in the nuclear fraction of brain, and heart tissue, using a colorimetric method. It was found that the expression and activity of PARP-1 was increased in brain tissue following PA. In heart, PARP-1activity was first increased 8 h, but then decreased 24 h after delivery in PA, as compared to control pups. In summary, the present results support the idea that PARP-1 overactivation is an underlying factor of the long term effects produced by PA, and that PARP-1 inhibition provides neuroprotection.
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