Beneficial effects of melatonin on morphological changes in postnatal cerebellar tissue owing to epileptiform activity during pregnancy in rats: Light and immunohistochemical study

Abstract

Although it has been demonstrated that maternal epilepsy has some harmful effects on newborn individuals, current data concerning the effects of epileptic phenomena in pregnant mothers on newborn pups are still limited. This study was undertaken to investigate the changes in the cerebellum of newborns of pinealectomized rats subjected to experimental epilepsy during pregnancy. In our study, the rats were randomly divided into six groups: intact control group, anesthesia control group, epilepsy group, melatonin-treated epileptic group, surgical pinealectomy group, and group of melatonin treatment following pinealectomy procedure. At 1 month after pinealectomy, an acute grand mal epileptic seizure was induced by 400 IU penicillin-G administration into their intrahippocampal CA3 region during the 13th day of their pregnancy in all animals except intact control group. On the neonatal first day, pups were perfused transcardially and the cerebellums removed were processed for light microscopic and immunohistochemical studies. Normal migration and maturation were determined in the postnatal rat cerebellum in both intact control and anesthesia (ketamine–xylazine) control groups, but the morphological structure of cerebellum in the epilepsy control group corresponded to the early embryonal period. It was found that experimental epilepsy or pinealectomy procedure enhanced nestin immunoreactivity, but exogenous melatonin treatment (30 μg/100 g body weight, i.p.) following pinealectomy inhibited increased nestin expression induced by melatonin deprival in vermis region of newborn rat cerebellum (P < 0.001). Our results confirm that epileptic seizures during pregnancy may impair neurogenesis and neuronal maturation in newborns, which are more dramatic in the presence of melatonin deficiency during pregnancy, explaining more harmful effects of epileptic seizures to embryos of aged mothers. To the best of our knowledge, this is the first study reporting the effects of maternal epilepsy during pregnancy in pinealectomized rats on nestin immunoexpression in the newborn rat cerebellum.