Effect of early-life stress on LINE-1 in animal model of child neglect

Abstract

The need for objective methods to assess child neglect has intensified. However, no biological indicators have been established for this purpose. Recently, early-life environments such as maternal attachment have been shown to affect the activity of long-interspersed nuclear element-1 (LINE-1, L1) in human infants and mouse pups. Herein, we hypothesized that the L1 copy number may correlate with the duration of neglect stress. To test this hypothesis, we employed a well-established mouse model of maternal separation that simulates early-life neglect. C57BL6/J mouse pups were subjected to daily maternal separation for either three or 6 h for two weeks from postnatal day (PND) one. We minimized the potential confounding effects of variations in maternal care by designating half of the littermates as untreated controls. L1 copy number in DNA extracted from the hippocampus and amygdala tissues at PND15 was quantified using real-time PCR with two different genes (5s-rRNA and Pthlh) as references. The results showed significantly higher L1 copy numbers in the hippocampus of pups separated for 6 h than in untreated controls. In addition, maternal separation duration was found to be correlated with L1 copy number in the hippocampus (r = 0.46, p < 0.001). Furthermore, the amplification of L1 in the hippocampus induced by 6 h of maternal separation was sustained until PND60. This study introduced a novel approach to understanding neglect-related L1 activity and highlighted the potential of L1 elements as an indicator in forensic medicine.