Department of Psychology, University of Wisconsin-Madison, United States.
Molecular and Cellular Pharmacology Training Program, University of Wisconsin-Madison, United States.
Brain Res. 2020 Dec 1;1748:147123. doi: 10.1016/j.brainres.2020.147123. Epub 2020 Sep 12.
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.
长散布元件 1（Line1）-一种逆转录转座子，占人类基因组的约 17%和大鼠基因组的约 24%-在精神疾病中表达异常，如精神分裂症、双相情感障碍和雷特综合征，表明它可能在神经发育中发挥重要作用。像 Line1 这样的逆转录转座子具有通过反转录自我复制的能力，并且随后可以重新插入整个基因组中，从而潜在地增加遗传多样性。我们试图了解早期生活应激（ELS）是否会影响 Line1 的表达和 DNA 拷贝数，ELS 是人类日后发生精神疾病的已知风险因素。我们的研究使用新生期捕食者气味暴露（POE）范式来模拟大鼠中的 ELS。我们发现，POE 诱导应激后，Line1 开放阅读框 1（ORF1）和 ORF2mRNA 均出现性别和区域特异性增加。有趣的是，ELS 增加了雄性海马体中的 Line1 DNA 拷贝数。这些数据表明，早期生活应激可能以性别和区域特异性的方式动员 Line1，导致大脑细胞之间的基因组异质性，表明一些细胞的遗传组成可能与其他细胞不同，从而导致基因组异质性。
