Angélica Torres-Berrío1, Alice Morgunova2, Michel Giroux3, Santiago Cuesta3, Eric J Nestler4, Cecilia Flores5. 1. 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. 2. Integrated Program in Neuroscience, McGill University, Montréal, Québec, Canada; Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada. 3. Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada. 4. 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. 5. Department of Psychiatry, McGill University, Montréal, Québec, Canada; Douglas Mental Health University Institute, McGill University, Montréal, Québec, Canada. Electronic address: cecilia.flores@mcgill.ca.
Abstract
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.
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.
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