MiR-182-5p: A Novel Biomarker in the Treatment of Depression in CSDS-Induced Mice

Int J Neuropsychopharmacol. 2024 Jan 1;27(1):pyad064. doi: 10.1093/ijnp/pyad064.


Background: Depression is a neuropsychiatric disease with a high disability rate and mainly caused by the chronic stress or genetic factors. There is increasing evidence that microRNAs (miRNAs) play a critical role in the pathogenesis of depression. However, the underlying molecular mechanism for the pathophysiology of depression of miRNA remains entirely unclear so far.

Methods: We first established a chronic social defeat stress (CSDS) mice model of depression, and depression-like behaviors of mice were evaluated by a series of behavioral tests. Next, we detected several abundantly expressive miRNAs suggested in previous reports to be involved in depression and found miR-182-5p was selected as a candidate for analysis in the hippocampus. Then western blotting and immunofluorescence were used together to examine whether adeno-associated virus (AAV)-siR-182-5p treatment alleviated chronic stress-induced decrease in hippocampal Akt/GSK3β/cAMP-response element binding protein (CREB) signaling pathway and increase in neurogenesis impairment and neuroinflammation. Furthermore, CREB inhibitor was adopted to examine if blockade of Akt/GSK3β/CREB signaling pathway abolished the antidepressant actions of AAV-siR-182-5p in mice.

Results: Knockdown of miR-182-5p alleviated depression-like behaviors and impaired neurogenesis of CSDS-induced mice. Intriguingly, the usage of agomiR-182-5p produced significant increases in immobility times and aggravated neuronal neurogenesis damage of mice. More importantly, it suggested that 666-15 blocked the reversal effects of AAV-siR-182-5p on the CSDS-induced depressive-like behaviors in behavioral testing and neuronal neurogenesis within hippocampus of mice.

Conclusions: These findings indicated that hippocampal miR-182-5p/Akt/GSK3β/CREB signaling pathway participated in the pathogenesis of depression, and it might give more opportunities for new drug developments based on the miRNA target in the clinic.

Keywords: CREB; Mechanism; MiR-182-5p; chronic social defeat stress; depression; neuronal neurogenesis.

MeSH terms

  • Animals
  • Behavior, Animal*
  • Cyclic AMP Response Element-Binding Protein / metabolism
  • Glycogen Synthase Kinase 3 beta / metabolism
  • Hippocampus
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Social Defeat
  • Stress, Psychological / metabolism


  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt
  • Cyclic AMP Response Element-Binding Protein
  • MicroRNAs