Neuroprotective effects of microRNA‐211‐5p on chronic stress‐induced neuronal apoptosis and depression‐like behaviours

• Published in: Journal of cellular and molecular medicine Vol. 25; no. 14; pp. 7028 - 7038
• Main Authors: Shen, Jie, Zhang, Ping, Li, Ye, Fan, Cuiqin, Lan, Tian, Wang, Wenjing, Yu, Shu Yan
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-07-2021; John Wiley and Sons Inc
• Subjects: Animals; Apoptosis; Brain; CA1 Region, Hippocampal - cytology; CA1 Region, Hippocampal - metabolism; CA1 Region, Hippocampal - physiopathology; CUMS; depression; Depression - genetics; Depression - metabolism; Dyrk Kinases; hippocampus; Homeostasis; Kinases; Male; MAP kinase; MAP Kinase Kinase 4 - genetics; MAP Kinase Kinase 4 - metabolism; MAP Kinase Kinase Kinase 5 - genetics; MAP Kinase Kinase Kinase 5 - metabolism; Mental depression; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; microRNA‐211‐5p; miRNA; Neurological diseases; Neurons - metabolism; Neuroprotection; Original; Pathogenesis; Protein Serine-Threonine Kinases - genetics; Protein Serine-Threonine Kinases - metabolism; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Rats; Rats, Wistar; Rodents; Signal Transduction; Stress; Stress, Psychological - genetics; Stress, Psychological - metabolism; Sucrose; Viruses; apoptosis; depression; hippocampus; CUMS; microRNA-211-5p
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.16716

Findings from recent studies have revealed that microRNAs (miRNAs) are related to numerous neurological disorders. However, whether miRNAs regulate neuronal anomalies involved in the pathogenesis of depression remain unclear. In the present study, we screened miRNA expression profiles in the CA1 hippocampus of a rat model of depression and found that a specific miRNA, microRNA‐211‐5p, was significantly down‐regulated in depressed rats. When miR‐211‐5p was up‐regulated in these rats, neuronal apoptosis within the CA1 area was suppressed, effects which were accompanied with an amelioration of depression‐like behaviours in these rats. These neuroprotective effects of miR‐211‐5p in depressed rats appear to result through suppression of the Dyrk1A/ASK1/JNK signalling pathway within the CA1 area. In further support of this proposal are the findings that knock‐down of miR‐211‐5p within the CA1 area of normal rats activated the Dyrk1A/ASK1/JNK pathway, resulting in the promotion of neuronal apoptosis and display of depression‐like behaviours in these rats. Taken together, these results demonstrate that deficits in miR‐211‐5p contribute to neuronal apoptosis and thus depression‐like behaviours in rats. Therefore, the miR‐211‐5p/Dyrk1A pathway may be critically involved in the pathogenesis of depression and serve as a potential therapeutic target for the treatment of depression.