کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5720591 1411319 2017 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Archival ReportDCC Confers Susceptibility to Depression-like Behaviors in Humans and Mice and Is Regulated by miR-218
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
Archival ReportDCC Confers Susceptibility to Depression-like Behaviors in Humans and Mice and Is Regulated by miR-218
چکیده انگلیسی

BackgroudVariations 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.MethodsWith 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.ResultsWe 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.ConclusionsThese 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.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biological Psychiatry - Volume 81, Issue 4, 15 February 2017, Pages 306-315
نویسندگان
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