Inverse changes in L1 retrotransposons between blood and brain in major depressive disorder.

Shu Liu,Zeyue Liu,Qi Xu,Tingfu Du,Yan Shen,Jianbo Xiu

doi:10.1038/srep37530

Abstract

Long interspersed nuclear element-1 (LINE-1 or L1) is a type of retrotransposons comprising 17% of the human and mouse genome, and has been found to be associated with several types of neurological disorders. Previous post-mortem brain studies reveal increased L1 copy number in the prefrontal cortex from schizophrenia patients. However, whether L1 retrotransposition occurs similarly in major depressive disorder (MDD) is unknown. Here, L1 copy number was measured by quantitative PCR analysis in peripheral blood of MDD patients (n = 105) and healthy controls (n = 105). The results showed that L1 copy number was increased in MDD patients possibly due to its hypomethylation. Furthermore, L1 copy number in peripheral blood and five brain regions (prefrontal cortex, hippocampus, amygdala, nucleus accumbens and paraventricular hypothalamic nucleus) was measured in the chronic unpredictable mild stress (CUMS) model of depression in mice. Intriguingly, increased L1 copy number in blood and the decreased L1 copy number in the prefrontal cortex were observed in stressed mice, while no change was found in other brain regions. Our results suggest that the changes of L1 may be associated with the pathophysiology of MDD, but the biological mechanism behind dysfunction of L1 retrotransposition in MDD remains to be further investigated.

Highlights

In this study, we quantified L1 copy number in peripheral blood genomic DNA and found that patients with Major depressive disorder (MDD) had a significant increase in L1 copy number
We further determined L1 copy number within 5 different brain regions involved in emotion regulation, including the prefrontal cortex (PFC), hippocampus, amygdala, nucleus accumbens (NAC) and paraventricular hypothalamic nucleus (PVN)
Quantitative multiplex polymerase chain reaction (PCR) to detect L1 copy number in the human brain regions and other tissues was first developed by Coufal et al.[12], which was widely used to evaluate the L1 copy number in neurological disorders such as Rett syndrome (RTT)[13] and schizophrenia[9]

Summary

Introduction

We quantified L1 copy number in peripheral blood genomic DNA and found that patients with MDD had a significant increase in L1 copy number. We quantified L1 copy number in the mouse model of depression (chronic unpredictable mild stress, CUMS), and found that CUMS mice had higher L1 copy number in peripheral blood than controls, consistent with results from MDD patients. We further determined L1 copy number within 5 different brain regions involved in emotion regulation, including the prefrontal cortex (PFC), hippocampus, amygdala, nucleus accumbens (NAC) and paraventricular hypothalamic nucleus (PVN). We found that L1 copy number in genomic DNA was different between blood and brain regions, and was decreased in PFC of stressed mice, while there were no significant changes in other brain regions

Methods

Results

Conclusion