Effect of prenatal pentylenetetrazol-induced kindling on learning and memory of male offspring

Current data concerning the effects of maternal seizure during pregnancy on newborns are limited. This study was carried out to investigate the effect of prenatal pentylenetetrazol (PTZ)-induced kindling on learning and memory of offspring. Female Wistar rats were kindled with i.p. injections of 25 mg/kg of PTZ on day 13 of their pregnancy. The spatial performance and passive avoidance learning of pups were tested at 7 weeks and 12 weeks of age using Morris water maze (MWM) task and shuttle-box apparatus, respectively. We found, for the first time, that prenatal exposure to maternal seizure induced by PTZ leads to a significant impairment of learning and memory. In addition, the number of live birth was significantly lower in kindled rats compared to control. In MWM studies, the young offspring of kindled rats had poor spatial learning ability. The frequent tonic-clonic seizures in pregnancy was also associated with a poor memory as evidenced by decrease in distance swam in the target quadrant by the offspring of the kindled mother in the adulthood. Data obtained from shuttle-box studies showed that retention latencies of pups born to kindled dams were significantly reduced compared to those born to control dams. The hippocampus, amygdala and frontal cortex are very important for memory consolidation and our data suggest that subsequent developmental events are not sufficient to overcome the adverse effects of prenatal exposure to maternal seizures to these regions of the brain. These observations may have clinical implications for cognitive and memory dysfunction associated with epilepsy during pregnancy.

Research Highlights▶ In this manuscript we have assessed the effects of prenatal exposure to the maternal seizure on the learning and memory of adolescent/young and adult male rats. ▶ We found, for the first time, that prenatal exposure to maternal tonic-clonic seizure significantly impairs spatial memory and passive avoidance learning. ▶ This finding provides a mechanistic link between maternal epilepsy and prenatal brain development and reveals a new aspect of PTZ modulation on learning and memory.