MicroRNA-139 modulates Alzheimer's-associated pathogenesis in SAMP8 mice by targeting cannabinoid receptor type 2

Genet Mol Res. 2017 Feb 16;16(1). doi: 10.4238/gmr16019166.


Alzheimer's disease (AD) is a neurodegenerative disorder, and is the most common type of dementia in the elderly population. Growing evidence indicates that microRNAs (miRNAs) play a crucial role in neuroinflammation associated with AD progression. In this study, we analyzed the expression of microRNA-139 (miR-139) as well as the learning and memory function in AD. We observed that the miR-139 expression was significantly higher in the hippocampus of aged senescence accelerated mouse prone 8 (SAMP8) mice (2.92 ± 0.13) than in the control mice (1.49 ± 0.08). Likewise, the overexpression of miR-139 by means of hippocampal injection impaired the hippocampus-dependent learning and memory formation. In contrast, the downregulation of miR-139 in mice improved learning and memory function in the mice. The level of cannabinoid receptor type 2 (CB2), a potential target gene of miR-139, was inversely correlated with the miR-139 expression in primary hippocampal cells. Furthermore, we demonstrated that miR-139 inversely modulated the responses to proinflammatory stimuli. Together, our findings demonstrate that miR-139 exerts a pathogenic effect in AD by modulating CB2-meditated neuroinflammatory processes.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism
  • Alzheimer Disease / psychology*
  • Animals
  • Cells, Cultured
  • Cytokines / metabolism
  • Disease Models, Animal
  • Gene Expression Regulation
  • Hippocampus / cytology*
  • Hippocampus / metabolism
  • Hippocampus / pathology
  • Humans
  • Maze Learning
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Receptor, Cannabinoid, CB2 / genetics*
  • Receptor, Cannabinoid, CB2 / metabolism


  • Cytokines
  • MIRN139 microRNA, mouse
  • MicroRNAs
  • Receptor, Cannabinoid, CB2