The Mechanism of miR-124 in Depression
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1)Health Science Center, Ningbo University, Zhejiang Provincial Key Laboratory of Pathophysiology, Ningbo 315211, China;2)The Affiliated Kangning Hospital of Ningbo University, Ningbo 315201, China

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This work was supported by grants from the Natural Science Foundation of Zhejiang Province (LY23H090003), Ningbo Science and Technology Plan Project (2022S021), National 111 Project of China (D16013), the Student Research and Innovation Program (2023SRIP1934), and K.C. Wong Magna Fund in Ningbo University.

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    Abstract:

    Depression is a prevalent mental illness worldwide, its multifaceted pathogenesis is still in the exploratory stage. MicroRNA (miRNA), as a crucial epigenetic regulator, plays an important role in depression. miR-124 is one of the most abundant miRNAs in the central nervous system including neurons and microglia, and involved in various biological events like neuron development and differentiation, synaptic and axonal growth, neural plasticity, inflammation and autophagy. Recent studies have reported abnormal expression of miR-124 in both depression patients and animal models. Most of the studies showed that miR-124 is upregulated in the hippocampus or prefrontal cortex in stress-induced rodent depression animal models such as CUMS, CSDS, CORT, CRS and LH but some evidence for divergence. Upregulation of miR-124 expression may be involved in depression-like behavior via CREB/BDNF/TrkB pathway, GR pathway, SIRT1 pathway, apoptosis and autophagy pathways by directly targeting these genes including Creb, Bdnf, Sirt1, Nr3c1, Ezh2 and Stat3. The downregulation of miR-124 expression in neurons is mainly involved in the neurogenesis and neuroplasticity impairments in depression by targeting the Notch signaling pathway and DDIT4/TSC1/2/mTORC1 pathway. The downregulation of miR-124 expression also was found in the activated microglia in the stress-induced models, and resulted in neuroinflammation. In summary, the abnormal expression of miR-124 in the brain of depression-related models and its related mechanisms are complex and even contradictory, and still need further research. This review provides a summary of the research progress of miR-124 in depression.

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XUE Yan, LI De-Zhu, XIE Hui-Ying, JIANG Chuan-Miao, ZHANG Jun-Fang. The Mechanism of miR-124 in Depression[J]. Progress in Biochemistry and Biophysics,2024,51(6):1316-1326

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History
  • Received:August 16,2023
  • Revised:May 19,2024
  • Accepted:December 19,2023
  • Online: July 30,2024
  • Published: June 20,2024