Prangos ferulacea (L.) ameliorates behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid

Brain Behav. 2023 Nov;13(11):e3224. doi: 10.1002/brb3.3224. Epub 2023 Aug 18.

Abstract

Background: Prenatal exposure to valproic acid (VPA) may enhance the risk of autism spectrum disorder (ASD) in children. This study investigated the effect of Prangos ferulacea (L.) on behavioral alterations, hippocampal oxidative stress markers, and apoptotic deficits in a rat model of autism induced by valproic acid.

Methods: Pregnant rats received VPA (600 mg/kg, intraperitoneally [i.p.]) or saline on gestational day 12.5 (E 12.5). Starting from the 30th postnatal day (PND 30), the pups were i.p. administered Prangos ferulacea (PF, 100 and 200 mg/kg), or the vehicle, daily until PND 58. On PND 30 and 58, various behavioral tasks were used to evaluate pups, including the open field, elevated plus-maze, hot-plate, and rotarod test. On PND 65, the animals were euthanized, and their brains were removed for histopathological and biochemical assay.

Results: Prenatal exposure to VPA caused significant behavioral changes in the offspring, reversed by administering an extract of Prangos ferulacea (L.). Additionally, prenatal VPA administration resulted in increased levels of malondialdehyde and deficits in antioxidant enzyme activities in the hippocampus, including catalase and glutathione, ameliorated by PF. Likewise, postnatal treatment with PF improved VPA-induced dysregulation of Bax and Blc2 in the hippocampus and reduced neuronal death in CA1, CA3, and dentate gyrus.

Conclusion: The findings of this study suggest that postnatal administration of PF can prevent VPA-induced ASD-like behaviors by exhibiting antiapoptotic and antioxidant properties. Therefore, PF may have the potential as an adjunct in the management of ASD.

Keywords: Prangos ferulacea (L.); autism; hippocampus; oxidative stress; valproic acid.

MeSH terms

  • Animals
  • Antioxidants / pharmacology
  • Autism Spectrum Disorder*
  • Autistic Disorder* / chemically induced
  • Autistic Disorder* / drug therapy
  • Behavior, Animal / physiology
  • Child
  • Disease Models, Animal
  • Female
  • Hippocampus / pathology
  • Humans
  • Oxidative Stress
  • Pregnancy
  • Prenatal Exposure Delayed Effects* / chemically induced
  • Prenatal Exposure Delayed Effects* / drug therapy
  • Prenatal Exposure Delayed Effects* / pathology
  • Rats
  • Rats, Wistar
  • Social Behavior
  • Valproic Acid

Substances

  • Valproic Acid
  • Antioxidants