S-adenosyl methionine prevents ASD like behaviors triggered by early postnatal valproic acid exposure in very young mice

Asher Ornoy, Liza Weinstein-Fudim, Matanel Tfilin, Zivanit Ergaz, Joseph Yanai, Moshe Szyf, Gadi Turgeman

Research output: Contribution to journalArticlepeer-review


Introduction: A common animal model of ASD is the one induced by valproic acid (VPA), inducing epigenetic changes and oxidative stress. We studied the possible preventive effect of the methyl donor for epigenetic enzymatic reactions, S-adenosine methionine (SAM), on ASD like behavioral changes and on redox potential in the brain and liver in this model. Methods: ICR albino mice were injected on postnatal day 4 with one dose of 300 mg/kg of VPA, with normal saline (controls) or with VPA and SAM that was given orally for 3 days at the dose of 30 mg/kg body weight. From day 50, we carried out neurobehavioral tests and assessment of the antioxidant status of the prefrontal cerebral cortex, liver assessing SOD and CAT activity, lipid peroxidation and the expression of antioxidant genes. Results: Mice injected with VPA exhibited neurobehavioral deficits typical of ASD that were more prominent in males. Changes in the activity of SOD and CAT increased lipid peroxidation and changes in the expression of antioxidant genes were observed in the prefrontal cortex of VPA treated mice, more prominent in females, while ASD like behavior was more prominent in males. There were no changes in the redox potential of the liver. The co-administration of VPA and SAM alleviated most ASD like neurobehavioral symptoms and normalized the redox potential in the prefrontal cortex. Conclusions: Early postnatal VPA administration induces ASD like behavior that is more severe in males, while the redox status changes are more severe in females; SAM corrects both. VPA-induced ASD seems to result from epigenetic changes, while the redox status changes may be secondary.

Original languageEnglish
Pages (from-to)64-74
Number of pages11
JournalNeurotoxicology and Teratology
StatePublished - 1 Jan 2019


  • ASD
  • Epigenetics
  • Mice
  • Postnatal injection
  • SAM
  • VPA

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience


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