Integrated Program in Neuroscience, McGill University, Montréal, Québec, Canada; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York.
Integrated Program in Neuroscience, McGill University, Montréal, Québec, Canada; Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada.
Biol Psychiatry. 2021 May 1;89(9):911-919. doi: 10.1016/j.biopsych.2020.10.015. Epub 2020 Nov 2.
Adolescence is a period of increased vulnerability to psychiatric disorders, including depression. Discovering novel biomarkers to identify individuals who are at high risk is very much needed. Our previous work shows that the microRNA miR-218 mediates susceptibility to stress and depression in adulthood by targeting the netrin-1 guidance cue receptor gene Dcc in the medial prefrontal cortex (mPFC).
Here, we investigated whether miR-218 regulates Dcc expression in adolescence and could serve as an early predictor of lifetime stress vulnerability in male mice.
miR-218 expression in the mPFC increases from early adolescence to adulthood and correlates negatively with Dcc levels. In blood, postnatal miR-218 expression parallels changes occurring in the mPFC. Notably, circulating miR-218 levels in adolescence associate with vulnerability to social defeat stress in adulthood, with high levels associated with social avoidance severity. Indeed, downregulation of miR-218 in the mPFC in adolescence promotes resilience to stress in adulthood.
miR-218 expression in adolescence may serve both as a marker of risk and as a target for early interventions.
青春期是精神疾病（包括抑郁症）易感性增加的时期。非常需要发现新的生物标志物来识别处于高风险的个体。我们之前的工作表明，microRNA miR-218 通过靶向内侧前额叶皮层（mPFC）中的神经导向因子 netrin-1 受体基因 Dcc，介导成年期的应激和抑郁易感性。
在这里，我们研究了 miR-218 是否在青春期调节 Dcc 的表达，并可能作为雄性小鼠一生中应激易感性的早期预测指标。
mPFC 中的 miR-218 表达从青春期早期到成年期增加，并与 Dcc 水平呈负相关。在血液中，产后 miR-218 的表达与 mPFC 中发生的变化平行。值得注意的是，青春期循环 miR-218 水平与成年期社交挫败应激的易感性相关，高水平与社交回避严重程度相关。事实上，mPFC 中 miR-218 的下调在青春期促进了成年期的应激抵抗。
青春期的 miR-218 表达可能既是风险的标志物，也是早期干预的靶点。
