Journal
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY
Volume 79, Issue -, Pages 417-425Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pnpbp.2017.07.024
Keywords
microRNA (miRNA); Brain-derived neurotrophic factor (BDNF); Depression; Hippocampus; Glucocorticoid receptor (GR)
Funding
- National Natural Science Foundation of China [81202940]
- Science Research Foundation of Ministry of Health & United Fujian Provincial Health and Education Project for Tracking the Key Research [WKJ-FJ-31]
- Promotion Program for Young and Middle-aged Teacher in Science and Technology Research of Huaqiao University [ZQN-PY218]
- Outstanding Youth Scientific Research Training Program in Colleges and Universities of Fujian Province [JA14015]
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Dysregulation of microRNA (miRNA) has been shown to be involved in early observations of depression. MicroRNA-124-3p (miR-124) is the most abundant microRNA in the brain. Previous studies have shown that miR-124 plays a major role in depression. Here we showed that miR-124 directly targeted glucocorticoid receptor (GR) in HEK 293 cells. In addition, inhibition of miR-124 by its antagomir (2 nmol/every two days) could reverse the decrease of sucrose preference and the increase of immobility time in mice exposed to chronic corticosterone (CORT, 40 mg/kg) injection. Moreover, these effects on behavioral improvement were coupled to the activation of brain-derived neurotrophic factor (BDNF), TrkB, ERK, and CREB, as well as the induction of synaptogenesis and neuronal proliferation. Altogether, our study suggests that miR-124 can be served as a biomarker for depression and a novel target for drug development, and demonstrates that inhibition of miR-124 may be a strategy for treating depression by activating BDNF-TrkB signaling pathway in the hippocampus.
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