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Abstract:
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The present study shows that nicotinamide
prevents the long-term eVect of perinatal asphyxia on
dopamine release monitored with in vivo microdialysis
in the neostriatum of 3-month-old rats. Perinatal
asphyxia was induced by immersing foetuses-containing
uterine horns removed from ready-to-deliver rats into a
water bath for 16 or 20 min. Sibling, spontaneous, and
caesarean-delivered pups were used as controls. Saline
or nicotinamide (0.8 mmol/kg, i.p.) was administered to
control and asphyxia-exposed animals 24, 48, and 72 h
after birth. After weaning, the rats were randomly distributed
in laboratory cages for animal care under standard
ad libitum laboratory conditions. Approximately
3 months after birth, control and asphyxia-exposed animals
were implanted with microdialysis probes into the
lateral neostriatum for measuring extracellular monoamine
and metabolite levels with HPLC-coupled to an
electrochemical detection system under basal, Damphetamine,
and K+-depolarising conditions. There
was an asphyxia-dependent decrease of extracellular
dopamine levels, mainly observed during the periods
when D-amphetamine (100 M) or KCl (100 mM) was
added into the perfusion medium. Compared to that
observed in caesarean-delivered controls, the eVect of
D-amphetamine on dopamine levels was decreased by
approximately 30 and 70% in animals exposed to 16 and
20 min of perinatal asphyxia, respectively. The eVect of
K+-depolarisation was decreased by 45 and 83% in animals
exposed to the same periods of asphyxia, respectively.
Both eVects were prevented by nicotinamide,
even if the treatment started 24 h after the insult. The
present results support the idea of nicotinamide as an
interesting molecule, useful for protecting against
anoxia/ischemia occurring at neonatal stages. Nicotinamide
can help to restore NADH/NAD+ depletion, but
also to inhibit PARP-1 overactivation, a mechanism of
action that has attracted attention, representing a novel
target for neuroprotection following insults involving
energy failure. |