Early life stress increases Line1 within the developing brain in a sex-dependent manner.

Abstract:

Long-interspersing element 1 (Line1)-a retrotransposon that comprises ~17% of the human genome and ~24% of the rat genome -is aberrantly expressed in psychiatric disorders such as schizophrenia, bipolar disorder, and Rett syndrome, suggesting it may play an important role in neurodevelopment. Retrotransposons such as Line1 have the ability to self-replicate via reverse transcription and can subsequently be reinserted throughout the genome, potentially increasing genetic diversity. We sought to understand whether early life stress (ELS), a known risk factor for the development of later psychiatric disorders in humans, would affect Line1 expression and DNA copy number. Our study uses a neonatal predator odor exposure (POE) paradigm to model ELS in rats. We found sex- and region-specific increases in both Line1 Open Reading Frame 1 (ORF1) and ORF2 mRNA following POE-induced stress. Interestingly, ELS increased Line1 DNA copy number within the male hippocampus. These data suggest the possibility that early life stress can mobilize Line1 in a sex- and region-specific manner, resulting in genomic heterogeneity between cells in the brain suggesting that some cells may have a different genetic makeup than others resulting in genomic heterogeneity.