National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences &Neuroscience Center, Chinese Academy of Medical Sciences and Peking Union Medical College, Tsinghua University, Beijing, 10005, China.
Institute of Medical Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Kunming, 650118, China.
Sci Rep. 2016 Nov 22;6:37530. doi: 10.1038/srep37530.
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.
长散在核元件-1（LINE-1 或 L1）是一种逆转录转座子，占人类和小鼠基因组的 17%，已被发现与几种类型的神经紊乱有关。先前的尸检大脑研究表明，精神分裂症患者前额叶皮层中的 L1 拷贝数增加。然而，L1 逆转座是否同样发生在重度抑郁症（MDD）中尚不清楚。在这里，通过定量 PCR 分析测量了 MDD 患者（n=105）和健康对照组（n=105）外周血中的 L1 拷贝数。结果表明，MDD 患者的 L1 拷贝数增加可能是由于其低甲基化。此外，还在慢性不可预测轻度应激（CUMS）抑郁小鼠模型中测量了外周血和五个脑区（前额叶皮层、海马体、杏仁核、伏隔核和室旁下丘脑核）中的 L1 拷贝数。有趣的是，在应激小鼠中观察到血液中 L1 拷贝数增加和前额叶皮层中 L1 拷贝数减少，而其他脑区没有变化。我们的结果表明，L1 的变化可能与 MDD 的病理生理学有关，但 L1 逆转座功能障碍在 MDD 中的生物学机制仍有待进一步研究。
