DCC confers susceptibility to depression-like behaviors in humans and mice and is regulated by miR-218

Torres-Berrío, Angélica, Lopez, Juan Pablo, Bagot, Rosemary C., Nouel, Dominique, Dal Bo, Gregory, Cuesta, Santiago, Zhu, Lei, Manitt, Colleen, Eng, Conrad, Cooper, Helen M., Storch, Kai-Florian, Turecki, Gustavo, Nestler, Eric J. and Flores, Cecilia (2017) DCC confers susceptibility to depression-like behaviors in humans and mice and is regulated by miR-218. Biological Psychiatry, 81 4: 306-315. doi:10.1016/j.biopsych.2016.08.017

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Author Torres-Berrío, Angélica
Lopez, Juan Pablo
Bagot, Rosemary C.
Nouel, Dominique
Dal Bo, Gregory
Cuesta, Santiago
Zhu, Lei
Manitt, Colleen
Eng, Conrad
Cooper, Helen M.
Storch, Kai-Florian
Turecki, Gustavo
Nestler, Eric J.
Flores, Cecilia
Title DCC confers susceptibility to depression-like behaviors in humans and mice and is regulated by miR-218
Formatted title
DCC confers susceptibility to depression-like behaviors in humans and mice and is regulated by miR-218
Journal name Biological Psychiatry   Check publisher's open access policy
ISSN 0006-3223
1873-2402
Publication date 2017-02-15
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.biopsych.2016.08.017
Open Access Status File (Author Post-print)
Volume 81
Issue 4
Start page 306
End page 315
Total pages 10
Place of publication Philadelphia, PA, United States
Publisher Elsevier
Collection year 2018
Language eng
Formatted 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.
Keyword Chronic social defeat stress
Guidance cue
Major depressive disorder
MicroRNA
Neurodevelopment
Resilience
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
 
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Created: Fri, 13 Jan 2017, 20:16:16 EST by Kirstie Asmussen on behalf of School of Music