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

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.

Retrotransposon-induced mosaicism in the neural genome

“…Here, we consider association as a study having shown that a retrotransposon insertion, or insertions, may cause a disease, or the study having reported elevation of retrotransposon copy number or mRNA level in the brain tissue of affected individuals when compared with healthy individuals. retrotransposon neurological disease insertions activity (mRNA levels, CNV, biomarkers) HERV multiple sclerosis [ 166 – 168 ] 3q13.31 microdeletion syndrome [ 169 ] amyotrophic lateral sclerosis [ 170 , 171 ] multiple sclerosis [ 166 – 168 , 172 ] schizophrenia [ 173 – 176 ] bipolar disorder [ 173 , 175 , 177 ] HIV-associated dementia [ 178 ] major depression [ 177 ] autism [ 179 ] ADHD [ 180 ] L1 pyruvate dehydrogenase complex deficiency [ 110 ] Fukuyama-type congenital muscular dystrophy [ 181 ] neurofibromatosis type I [ 182 ] ataxia with oculomotor apraxia 2 [ 183 ] glioblastoma [ 184 , 185 ] schizophrenia [ 176 ] ataxia telangiectasia [ 54 ] Coffin Lowry syndrome [ 186 ] major depression [ 187 , 188 ] schizophrenia [ 187 – 189 ] Rett syndrome [ …”

A Possible Role for Long Interspersed Nuclear Elements-1 (LINE-1) in Huntington’s Disease Progression

“…Growing evidence suggests that the roles of retrotransposable elements underlie progression of multiple neuronal diseases [ 15 , 16 ]. Here, we report that the caudate genome of the Huntington’s disease mouse model exhibits increased copies of L1 retrotransposon and are associated with the increased transcription of its transcripts, ORF1 and ORF2.…”

“…The L1 content was evaluated as copy number content of ORF1 and ORF2 in brain and liver tissues samples of both HD transgenic and control mice. The method used to determine the L1 content was followed as described previously with minor modifications [ 15 , 19 ]. Briefly, 500 pg of DNA was used as a template and was amplified using m5′UTR-, mORF1-, and mORF2-specific primer sets in an SYBR green assay.…”

“…Recent studies have suggested that mobile elements in the genome such as long interspersed nuclear elements-1 (LINE-1 or L1) are modified in a tissue-specific way and are associated with the pathology of multiple neurological diseases such as schizophrenia and major depressive disorder [ 15 , 16 ]. In addition, alterations in the L1 content of tissues are known to affect the expression of its 2 ORFs (ORF1 and ORF2), which could affect the signaling pathways to facilitate disease progression [ 17 ].…”

Noncoding RNAs: Stress, Glucocorticoids, and Posttraumatic Stress Disorder

“…Other observations have confirmed the expression of transposons in the brains of healthy and stressed rodents, primates, and humans under normal conditions. Changes in their expression occur in many disorders of the nervous system, including amyotrophic lateral sclerosis, depression, and schizophrenia (108)(109)(110)(111)(112)(113)(114). Thus, the importance of these elements to understand complex disorders such as PTSD is apparent (115,116).…”