Evaluation of the Therapeutic Potential of Prenatal Morin Supplementation on Valproic Acid-Induced Autism in Offspring of Epileptic Pregnant Wistar Rats

Abstract

Anti-epileptic drugs such as valproic acid (VPA) have been reported to have detrimental effects on the offspring of women with epilepsy (WWE). This study investigated the effects of prenatal morin supplementation on the hippocampus of a rat model of autism, prenatally induced by VPA. The pups of adult female kindled and non-kindled rats were used for this study. Pregnant rats were randomly assigned to five groups (n=6): Non-kindled rats’ pups were assigned as the control group and received normal saline (mL/kg). The kindled rats were allowed to mate fourteen days after kindling and were separated into groups as follows: pentylenetetrazol (PTZ), PTZ+VPA, PTZ+VPA+morin, and PTZ+VPA+folic acid. Treatments were carried out on gestational days 8–18. Following delivery and weaning on postnatal day 32, neurobehavioural studies were conducted. Results showed that in-utero morin supplementation improved all VPA-induced behavioural and cognitive deficits in the offspring of kindled Wistar rats. Furthermore, prenatal VPA increased malondialdehyde and nitrite levels, and deficits in antioxidant enzyme activities in the hippocampus, which were attenuated by morin supplementation. VPA-induced increases in neuroinflammatory markers and decreases in brain derived neurotrophic factor (BDNF) levels were reversed by morin treatment. Prenatal morin supplementation also exhibited neuroprotection against VPA-induced hippocampal neuronal damages, as seen in the preserved hippocampal neural architecture of the morin-treated groups. These findings showed that prenatal administration of morin prevented valproic acid-induced autistic-like behaviour in the offspring of WWE. This could be attributed to the augmentation of the oxido-inflammatory system and neuro-protective defence mechanisms via upregulation of BDNF in the brain.