Perinatal supplementation with omega-3 fatty acids corrects the aberrant social and cognitive traits observed in a genetic model of autism based on FMR1 deletion in rats

Nutr Neurosci. 2022 May;25(5):898-911. doi: 10.1080/1028415X.2020.1819107. Epub 2020 Sep 11.


Background and objective: Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder for which no treatments exist. Fragile X syndrome (FXS) is the most common form of inherited mental retardation and the most frequent monogenic cause of ASD. Given the lack of pharmacological treatments for ASD, increasing interest is devoted to non-pharmacological approaches, including dietary interventions. Omega-3 polyunsaturated fatty acids (PUFAs) are critical for neurobehavioraldevelopment. This study had two aims: 1. To validatethe recently developed Fmr1-Δexon 8 rat model of FXS; 2. To assess the impact of omega-3 PUFAs dietary supplementation during pregnancy and lactation on the altered behavior displayed by Fmr1-Δexon 8 rats.Methods: Female Fmr1-Δexon 8 and wild-type Sprague-Dawley rats were fed with either an omega-3 PUFAs enriched diet or with an isocaloric control diet during pregnancy and lactation. Behavioral experiments were carried out on the infant (Postnatal days (PNDs) 9 and 13), juvenile (PND 35) and adult (PND 90) male offspring.Results: Fmr1-Δexon 8 pups showed hypolocomotion, reduced ultrasonic vocalizations (USVs) emission and impaired social discrimination compared to wild-type controls. Juvenile and adult Fmr1-Δexon 8 rats showed deficits in the social and cognitive domains, that were counteracted by perinatal omega-3 PUFAs supplementation.Conclusion: Our results support the validity of the Fmr1-Δexon 8 rat model to mimic key autistic-like features and support an important role of omega-3 PUFAs during of neurodevelopment. Although the mechanisms underlying the beneficial effects of omega-3 PUFAs supplementation in ASD needs to be clarified, this dietary intervention holds promise to mitigate core and comorbid autistic features.

Keywords: Omega-3 PUFAs; autism; behavior; dietary supplementation; fragile X syndrome; rats.

MeSH terms

  • Animals
  • Autism Spectrum Disorder* / prevention & control
  • Autistic Disorder* / prevention & control
  • Cognition
  • Dietary Supplements
  • Fatty Acids, Omega-3*
  • Female
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Syndrome* / genetics
  • Humans
  • Male
  • Models, Genetic
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley


  • FMR1 protein, human
  • Fatty Acids, Omega-3
  • Fmr1 protein, rat
  • Fragile X Mental Retardation Protein