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Prog Neuropsychopharmacol Biol Psychiatry. 2017 Oct 3;79(Pt B):417-425. doi: 10.1016/j.pnpbp.2017.07.024. Epub 2017 Jul 29.

microRNA-124 targets glucocorticoid receptor and is involved in depression-like behaviors.

Author information

1
Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China; Institute of Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China.
2
Xiamen Hospital of Traditional Chinese Medicine, Xiamen 361009, Fujian Province, PR China.
3
Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China; Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen 361021, Fujian Province, PR China; Institute of Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China.
4
Department of Chemical and Pharmaceutical Engineering, College of Chemical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China; Fujian Provincial Key Laboratory of Biochemical Technology, Huaqiao University, Xiamen 361021, Fujian Province, PR China; Institute of Pharmaceutical Engineering, Huaqiao University, Xiamen 361021, Fujian Province, PR China. Electronic address: litaoyi@hqu.edu.cn.

Abstract

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 (2nmol/every two days) could reverse the decrease of sucrose preference and the increase of immobility time in mice exposed to chronic corticosterone (CORT, 40mg/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.

KEYWORDS:

Brain-derived neurotrophic factor (BDNF); Depression; Glucocorticoid receptor (GR); Hippocampus; microRNA (miRNA)

PMID:
28764913
DOI:
10.1016/j.pnpbp.2017.07.024
[Indexed for MEDLINE]

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