BACKGROUND 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). METHODS 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. RESULTS 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. CONCLUSIONS miR-218 expression in adolescence may serve both as a marker of risk and as a target for early interventions.

中文翻译：

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青春期的 miR-218 预测并调节对压力的脆弱性

背景技术青春期是对包括抑郁症在内的精神疾病的易感性增加的时期。非常需要发现新的生物标志物来识别高风险个体。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 netrin-1 指导线索受体基因 Dcc 来介导成年期对压力和抑郁的易感性。方法 在这里，我们研究了 miR-218 是否在青春期调节 Dcc 表达，并可以作为雄性小鼠终生压力脆弱性的早期预测因子。结果 mPFC 中 miR-218 的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，出生后 miR-218 表达与 mPFC 中发生的变化相似。尤其，青春期循环的 miR-218 水平与成年期对社交失败压力的脆弱性相关，高水平与社交回避的严重程度相关。事实上，青春期 mPFC 中 miR-218 的下调促进了成年期对压力的恢复。结论 青春期 miR-218 的表达既可以作为风险标志物，也可以作为早期干预的目标。