Prenatal maternal immune activation causes epigenetic differences in adolescent mouse brain

Area of Science:

• Neuroscience
• Epigenetics
• Developmental Biology

Background:

• Epigenetic alterations, including DNA methylation, are implicated in neurodevelopmental disorders like schizophrenia and autism.
• Prenatal inflammation is a recognized environmental risk factor for schizophrenia and related neurodevelopmental conditions.
• DNA methylation patterns can be influenced by environmental exposures during critical developmental periods.

Purpose of the Study:

• To investigate the hypothesis that prenatal inflammation alters DNA methylation in brain regions relevant to schizophrenia, specifically the striatum and hypothalamus.
• To examine global DNA methylation using repetitive elements (LINE1 and IAPs) and specific gene promoter methylation (Mecp2).

Main Methods:

• Mice were exposed to Poly(I:C) (viral mimic) or saline during gestation.
• Brain tissues (hypothalamus and striatum) were harvested from offspring at 6 weeks of age.
• Quantitative DNA methylation analysis was performed using the Sequenom EpiTYPER assay on LINE1, IAPs, and the Mecp2 promoter.

Main Results:

• Prenatal Poly(I:C) exposure led to significant global DNA hypomethylation in the hypothalamus, particularly in females.
• The Mecp2 gene promoter region in the hypothalamus was significantly hypomethylated following prenatal inflammation.
• No significant alterations in DNA methylation were observed in the striatum or for IAP elements in the hypothalamus.

Conclusions:

• This study provides the first experimental evidence linking prenatal inflammation to epigenetic changes, including Mecp2 promoter hypomethylation in the hypothalamus.
• These findings suggest that environmental risk factors (inflammation) and genetic factors may converge on common epigenetic pathways in neurodevelopmental disorders.
• The modifiable nature of epigenetic changes highlights potential therapeutic targets for neurodevelopmental conditions.