Prenatal hypoxia-ischemia alters expression and activity of nitric oxide synthase in the young rat brain and causes learning deficits

Inhibition of nitric oxide synthase (NOS) is known to possibly impair learn ing and memory, Our previous studies have demonstrated that prenatal hypoxi a-ischemia (HI) decreases NOS expression and NOS activity in the neonatal r at brain, To investigate whether effects of prenatal HI on NOS expression c ontinue and whether prenatal HI affects learning and memory in young rats, NOS expression and NOS activity were determined in the hippocampus of rat b rains at 28 days of age following a prenatal HI insult on G17. Performances in the passive avoidance test and the Morris water maze test were also stu died in these young rats prior to sampling. Rat fetuses were subjected to e ither a 30-min prenatal HI insult or a sham operation (SH) on gestation day 17 and rat pups were delivered naturally. Increased locomotor activity was observed in the prenatal HI rats as compared to the SH rats on postnatal d ays 13 and 15, but not on postnatal days 20 and 30, Prenatal HI affected le arning ability in these young rats at 28 days of age, as indicated by a del ayed acquisition of passive avoidance and by longer escape latency in the M orris water maze test as compared to the SH group. Prenatal HI did not affe ct retention of passive avoidance and spatial memory. Concomitant with thes e learning deficits, expression of neuronal NOS and endothelial NOS mRNAs a s well as Ca2+-depedent NOS activity in the hippocampus of the prenatal HI rat brain were significantly decreased as compared to the SH group, These r esults suggest that a 30-min prenatal HI insult on gestation day 17 in rats has long-lasting effects on NOS expression and NOS activity in the offspri ng brain and on learning ability of these young rats. The learning deficit in offspring is possibly associated with the reduction in expression of NOS mRNA and NOS activity in the hippocampus of these animals. (C) 1999 Elsevi er Science Inc.