22225
Prenatal Immune Activation Alters the Adult Neural Epigenome but Can be Partly Stabilized By a n-3 Polyunsaturated Fatty Acid Diet

Thursday, May 12, 2016: 2:52 PM
Hall B (Baltimore Convention Center)

ABSTRACT WITHDRAWN

Background:  

Prenatal exposure to Maternal Immune Activation (MIA) increases the risk of autism. The MIA rodent model permits direct experimental evaluation of the biological mechanisms driving this vulnerability. It also provides an opportunity to screen novel prevention strategies. 

Objectives:  

In this study we tested the hypotheses that MIA in the mouse model has wide-spread effects on the epigenome; and that these can be prevented by a post-weaning diet enriched with n-3 polyunsaturated fatty acids (PUFA).

Methods:  

Pregnant mice were exposed to intravenous PolyI:C (a viral analogue) or saline (control) on gestation day 9. Half the offspring were weaned using a conventional lab diet (n-6 PUFA); half had a n-3 PUFA enriched diet. Genome-wide DNA methylation in hypothalamic brain tissue was examined using Next Generation Sequencing techniques.

Results:  

Adult offspring exposed to MIA prenatally had significant global DNA hypomethylation. Pathway analyses revealed that genes regulating synaptic plasticity were differentially methylated following MIA. Moreover, DNA methylation differences were concentrated at risk loci linked to neurodevelopmental disorders. More than 80% of genes affected by MIA were ‘stabilized’ by the n-3 PUFA intervention.

Conclusions:  

Thus, MIA during prenatal life causes persistent widespread epigenetic changes in the postnatal brain that can be limited by early dietary intervention with n-3 PUFA. These effects on the epigenome may have functional consequences. For example, we have previously reported that the brain biochemical and behavioural consequences of MIA can also be prevented by n-3 PUFA diet. That the developmental impact of early life immune activation can be modified - especially by a relatively simple and low cost intervention – is a critical observation and deserves further study.