Angélica Torres-Berrío1, Juan Pablo Lopez2, Rosemary C Bagot3, Dominique Nouel4, Gregory Dal Bo5, Santiago Cuesta6, Lei Zhu4, Colleen Manitt4, Conrad Eng4, Helen M Cooper7, Kai-Florian Storch6, Gustavo Turecki8, Eric J Nestler9, Cecilia Flores10. 1. Integrated Program in Neuroscience, Montréal, Québec, Canada; Douglas Mental Health University Institute; Montréal, Québec, Canada. 2. Department of Human Genetics; Montréal, Québec, Canada; McGill Group for Suicide Studies, Montréal, Québec, Canada. 3. Departments of Psychology ; Montréal, Québec, Canada. 4. Douglas Mental Health University Institute; Montréal, Québec, Canada. 5. Douglas Mental Health University Institute; Montréal, Québec, Canada; Département de Toxicologie et risques chimiques, IRBA, Brétigny sur Orge, France. 6. Psychiatry, McGill University; Montréal, Québec, Canada; Douglas Mental Health University Institute; Montréal, Québec, Canada. 7. Queensland Brain Institute, The University of Queensland, Brisbane, Queensland, Australia. 8. Psychiatry, McGill University; Montréal, Québec, Canada; Douglas Mental Health University Institute; Montréal, Québec, Canada; McGill Group for Suicide Studies, Montréal, Québec, Canada. 9. Fishberg Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York. 10. Psychiatry, McGill University; Montréal, Québec, Canada; Douglas Mental Health University Institute; Montréal, Québec, Canada. Electronic address: cecilia.flores@mcgill.ca.
Abstract
BACKGROUD: Variations in the expression of the Netrin-1 guidance cue receptor DCC (deleted in colorectal cancer) appear to confer resilience or susceptibility to psychopathologies involving prefrontal cortex (PFC) dysfunction. METHODS: With the use of postmortem brain tissue, mouse models of defeat stress, and in vitro analysis, we assessed microRNA (miRNA) regulation of DCC and whether changes in DCC levels in the PFC lead to vulnerability to depression-like behaviors. RESULTS: We identified miR-218 as a posttranscriptional repressor of DCC and detected coexpression of DCC and miR-218 in pyramidal neurons of human and mouse PFC. We found that exaggerated expression of DCC and reduced levels of miR-218 in the PFC are consistent traits of mice susceptible to chronic stress and of major depressive disorder in humans. Remarkably, upregulation of Dcc in mouse PFC pyramidal neurons causes vulnerability to stress-induced social avoidance and anhedonia. CONCLUSIONS: These data are the first demonstration of microRNA regulation of DCC and suggest that, by regulating DCC, miR-218 may be a switch of susceptibility versus resilience to stress-related disorders.
BACKGROUD: Variations in the expression of the Netrin-1 guidance cue receptor DCC (deleted in colorectal cancer) appear to confer resilience or susceptibility to psychopathologies involving prefrontal cortex (PFC) dysfunction. METHODS: With the use of postmortem brain tissue, mouse models of defeat stress, and in vitro analysis, we assessed microRNA (miRNA) regulation of DCC and whether changes in DCC levels in the PFC lead to vulnerability to depression-like behaviors. RESULTS: We identified miR-218 as a posttranscriptional repressor of DCC and detected coexpression of DCC and miR-218 in pyramidal neurons of human and mouse PFC. We found that exaggerated expression of DCC and reduced levels of miR-218 in the PFC are consistent traits of mice susceptible to chronic stress and of major depressive disorder in humans. Remarkably, upregulation of Dcc in mouse PFC pyramidal neurons causes vulnerability to stress-induced social avoidance and anhedonia. CONCLUSIONS: These data are the first demonstration of microRNA regulation of DCC and suggest that, by regulating DCC, miR-218 may be a switch of susceptibility versus resilience to stress-related disorders.
Authors: Eric M Small; Lillian B Sutherland; Kartik N Rajagopalan; Shusheng Wang; Eric N Olson Journal: Circ Res Date: 2010-10-14 Impact factor: 17.367
Authors: Juan Pablo Lopez; Raymond Lim; Cristiana Cruceanu; Liam Crapper; Caroline Fasano; Benoit Labonte; Gilles Maussion; Jennie P Yang; Volodymyr Yerko; Erika Vigneault; Salah El Mestikawy; Naguib Mechawar; Paul Pavlidis; Gustavo Turecki Journal: Nat Med Date: 2014-06-08 Impact factor: 53.440
Authors: Santiago Cuesta; José Maria Restrepo-Lozano; Steven Silvestrin; Dominique Nouel; Angélica Torres-Berrío; Lauren M Reynolds; Andreas Arvanitogiannis; Cecilia Flores Journal: Neuropsychopharmacology Date: 2017-11-20 Impact factor: 7.853