Effects of ω-3 fatty acids on stereotypical behavior and social interactions in Wistar rats prenatally exposed to lipopolysaccarides

Nutrition. 2017 Mar;35:119-127. doi: 10.1016/j.nut.2016.10.019. Epub 2016 Nov 22.

Abstract

Objective: Supplementation with ω-3 polyunsaturated fatty acids (PUFAs) can positively contribute to neurologic development, modulating inflammatory responses, promoting homeostasis, and having a positive effect on animal behaviors associated with mental disorders. The aim of this study was to evaluate behavioral and biochemical effects of ω-3 fatty acid supplementation in an animal model for mental disorders by prenatal maternal exposure to lipopolysaccardies (LPS) from the maternal immune activation.

Methods: Twelve pregnant Wistar rats were used. Each rat received 100 μg/kg of LPS or saline solution on gestational day (GD) 9.5. The offspring remained with mothers until weaning and from postnatal day (PND) 30 were supplemented with ω-3 PUFA or saline solution by gavage at a dose of 0.8 g/kg orally for 21 d. On PND 52, the animals underwent behavioral tests; then, they were sacrificed, and the brain structures were dissected and analyzed by levels: neuron-specific enolase (NSE), brain-derived neurotrophic factor, and transforming growth factor (TGF)-β.

Result: Prenatal exposure to LPS significantly increased the episodes of stereotyped movements and decreased social interaction in the offspring (P = 0.009 and P = 0.001, respectively), after ω-3 PUFA supplementation these parameters reversed (P = 0.005 and P = 0.013, respectively). Significant changes also were identified in the biochemical analysis in NSE and TGF-β in the brain structures; these conditions were reversed after ω-3 PUFA supplementation.

Conclusion: Supplementation with ω-3 PUFA reversed animal behaviors that often are observed in autism and other mental disorders in rats prenatally exposed to LPS, and also exerted neuroprotective effects in marker levels of neuronal damage and expression of TGF-β.

Keywords: Lipopolysaccharides; Maternal immune activation; Neuron-specific enolase; Transforming growth factor-β; ω-3.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Dietary Supplements
  • Fatty Acids, Omega-3 / pharmacology*
  • Female
  • Interpersonal Relations*
  • Lipopolysaccharides / toxicity*
  • Male
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Rats, Wistar
  • Stereotyped Behavior / drug effects*
  • Transforming Growth Factor beta / genetics
  • Transforming Growth Factor beta / metabolism
  • Weaning

Substances

  • Brain-Derived Neurotrophic Factor
  • Fatty Acids, Omega-3
  • Lipopolysaccharides
  • Transforming Growth Factor beta