The therapeutic potential of S-adenosyl methionine (SAM) in a murine model for autism

Background: Autism Spectrum Disorder (ASD) is a developmental disorder that results in impaired cognitive and social functions. the etiology is considered to involve epigenetic changes. Indeed, an environmental model known for ASD is the developmental exposure to valproic acid (VPA), a known HDAC inhibitor that can induce DNA hypomethylation. We hypothesized that treating VPA exposed mice with the methyl donor S-adenosyl methionine can counteract the effect of VPA, even long after its initial exposure. We, therefore, subjected ICR mice to injection with 300 mg/kg of VPA at postnatal day 4. Control group was injected with saline. On postnatal day 25 until 50 the mice received 30 mg/kg/day SAM supplemented in their drinking water. At Post-natal days 21 and 50 behavioural tests were carried containing cognitive, social and motor skills in order to validate our model and to detect any changes or improvement following SAM treatment. Post-mortem molecular analysis for changes in hippocampal neurogenesis were performed by immunohistochemistry and real time PCR.
Results: our results indicate VPA exposure impairs post-natal development by reducing locomotor activity as early as day 21. VPA exposure increased cognitive rigidity and decreased sociability which were corrected by SAM treatment and affected overall autism-like behaviour. However, the effect of SAM was more prominent in females than in males. Impaired neurogenesis observed in both sexes was corrected in females but not in males following SAM treatment.
Conclusions: Collectively, the significance of the results of this study provide initial evidence for the therapeutic potential of SAM in ASD especially in females.