Role of Monocyte-Derived MicroRNA106b∼25 in Resilience to Social Stress.

TitleRole of Monocyte-Derived MicroRNA106b∼25 in Resilience to Social Stress.
Publication TypeJournal Article
Year of Publication2019
AuthorsPfau, ML, Menard, C, Cathomas, F, Desland, F, Kana, V, Chan, KL, Shimo, Y, LeClair, K, Flanigan, ME, Aleyasin, H, Walker, DM, Bouchard, S, Mack, M, Hodes, GE, Merad, MM, Russo, SJ
JournalBiol Psychiatry
Volume86
Issue6
Pagination474-482
Date Published2019 Sep 15
ISSN1873-2402
Abstract

BACKGROUND: Clinical studies suggest that heightened peripheral inflammation contributes to the pathogenesis of stress-related disorders, including major depressive disorder. However, the molecular mechanisms within peripheral immune cells that mediate enhanced stress vulnerability are not well known. Because microRNAs (miRs) are important regulators of immune response, we sought to examine their role in mediating inflammatory and behavioral responses to repeated social defeat stress (RSDS), a mouse model of stress vulnerability that produces susceptible and resilient phenotypes.

METHODS: We isolated Ly6c monocytes via fluorescence-activated cell sorting in the blood of susceptible and resilient mice following RSDS and profiled miR expression via quantitative real-time polymerase chain reaction. Bone marrow chimeric mice were generated to confirm a causal role of the miR-106b∼25 cluster in bone marrow-derived leukocytes in mediating stress resilience versus susceptibility.

RESULTS: We found that RSDS produces an increase in circulating Ly6c inflammatory monocytes in both susceptible and resilient mice. We next investigated whether intrinsic leukocyte posttranscriptional mechanisms contribute to individual differences in stress response and the resilient phenotype. Of the miRs profiled in our panel, eight were significantly regulated by RSDS within Ly6c monocytes, including miR-25-3p, a member of the miR-106b∼25 cluster. Selective knockout of the miR-106b∼25 cluster in peripheral leukocytes promoted behavioral resilience to RSDS.

CONCLUSIONS: Our results identify the miR-106b∼25 cluster as a key regulator of stress-induced inflammation and depression that may represent a novel therapeutic target for drug development.

DOI10.1016/j.biopsych.2019.02.023
Alternate JournalBiol. Psychiatry
PubMed ID31101319
PubMed Central IDPMC6717005
Grant ListR01 MH090264 / MH / NIMH NIH HHS / United States
R01 MH104559 / MH / NIMH NIH HHS / United States
R01 MH114882 / MH / NIMH NIH HHS / United States
F31 MH105217 / MH / NIMH NIH HHS / United States
P50 AT008661 / AT / NCCIH NIH HHS / United States
P50 MH096890 / MH / NIMH NIH HHS / United States
T32 MH096678 / MH / NIMH NIH HHS / United States
T32 MH087004 / MH / NIMH NIH HHS / United States