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1.
Sci Rep ; 11(1): 3549, 2021 02 11.
Article in English | MEDLINE | ID: mdl-33574362

ABSTRACT

Early life stress (ELS) has been shown to have a significant impact on typical brain development and the manifestation of psychological disorders through epigenetic modifications that alter gene expression. Line1, a retrotransposon associated with genetic diversity, has been linked with various psychological disorders that are associated with ELS. Our previous work demonstrated altered Line1 DNA copy number in the neonatal period following stressful experiences; we therefore chose to investigate whether early life stress altered Line1 retrotransposition persists into the juvenile period of development. Our study uses a neonatal predator odor exposure (POE) paradigm to model ELS in rats. We examined Line1 using qPCR to assess Line1 expression levels and DNA copy number in the male and female juvenile amygdala, hippocampus and prefrontal cortex-areas chosen for their association with affective disorders and stress. We report a sex difference in Line1 levels within the juvenile amygdala. We also find that ELS significantly increases Line1 DNA copy number within the juvenile amygdala which correlates with reduced juvenile social play levels, suggesting the possibility that Line1 may influence juvenile social development.


Subject(s)
Adverse Childhood Experiences , Brain/growth & development , Long Interspersed Nucleotide Elements/genetics , Stress, Psychological/genetics , Amygdala/growth & development , Amygdala/metabolism , Amygdala/pathology , Animals , Brain/pathology , DNA Copy Number Variations/genetics , Disease Models, Animal , Female , Hippocampus/metabolism , Hippocampus/pathology , Humans , Male , Prefrontal Cortex/metabolism , Prefrontal Cortex/pathology , Rats , Sex Characteristics , Stress, Psychological/pathology
2.
Brain Res ; 1748: 147123, 2020 12 01.
Article in English | MEDLINE | ID: mdl-32931818

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.


Subject(s)
Brain/metabolism , Long Interspersed Nucleotide Elements/genetics , Stress, Psychological/metabolism , Animals , Brain/growth & development , Female , Hippocampus/growth & development , Hippocampus/metabolism , Male , Open Reading Frames/genetics , Rats , Rats, Sprague-Dawley , Risk Factors , Sex Factors , Stress, Psychological/genetics
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