Dietary Intervention on the Epigenetic Changes Induced by Environmental Risk Factors in the Adolescent Brain

Abstract

Objectives: To identify the effect of early dietary intervention by omega-3 Poly-Unsaturated Fatty Acids (PUFAs) on Long Interspersed Elements- 1(LINE1) and Mecp2 methylation in regions relevant to schizophrenia, namely the dopamine rich Striatum and endocrine regulatory centre, the hypothalamus Methods: Differential epigenetic modifications at CpG dinucleotide modules were observed in the brain following exposure to maternal immune activation in a mouse model exhibiting abnormalities which are analogous to those found in schizophrenia and related conditions such as autism. We compared global DNA methylation using LINE1 assay and Mecp2 promoter methylation in brain tissue from 6 weeks old offspring of mice exposed to the viral analogue PolyI:C (affected group; n = 44 males; n = 24 females = 20) or saline (control group; n = 67 males; n = 27 females = 40) on gestation day 9. Half of the animals in each group got early dietary intervention with Omega-3 PUFAs. We employed Sequenom EpiTYPER to quantitatively analyze differences in DNA methylation levels utilizing promoter CpG methylation of LINE1 and Mecp2 Results: Prenatal exposure to PolyI:C was confirmed to cause significant LINE1 hypomethylation in the hypothalamus (ß estimate = -0.002, p = 0.009) but not in striatum, when compared to saline controls even after early dietary intervention with omega-3 PUFA. Omega-3 supplementation was effectively modulating LINE1 methylation in striatum (ß estimate = -0.011, p = 3.8x10-8) but not in hypothalamus. A significant hypomethylation of Mecp2 promoter (ß estimate = -0.027, p = 0.002) in hypothalamus and a marginally significant hypomethylation in striatum (ßestimate = -0.041, p = 0.065) was observed in PolyI:C group with a strong sex effect, namely more hypomethlyation in males. Omega-3 supplementation was effective on Mecp2 promoter methylation in hypothalamus (ß estimate = -0.083, p = 8.14x10-13) and striatum (ß estimate = -0.178, p = 6.52x10-10). A significant three way interaction was observed between polyI:C and omega-3 treatment and male group (ß estimate = 0.229, p = 0.038) with an improved Mecp2 methylation Conclusion: These results indicate that early dietary intervention modulates epigenetic changes caused by exposure to inflammation during prenatal life, especially hypomethylation of the Mecp2 promoter region in males Disclosure of Interest: None declared