NF-кB-regulated micro RNAs (miRNAs) in primary human brain cells

Exp Neurol. 2012 Jun;235(2):484-90. doi: 10.1016/j.expneurol.2011.11.022. Epub 2011 Nov 23.


Micro RNAs (miRNAs), small and labile ~22 nucleotide-sized fragments of single stranded RNA, are important regulators of messenger (mRNA) complexity and in shaping the transcriptome of a cell. In this communication, we utilized amyloid beta 42 (Aβ42) peptides and interleukin-1beta (IL-1β) as a combinatorial, physiologically-relevant stress to induce miRNAs in human primary neural (HNG) cells (a co-culture of neurons and astroglia). Specific miRNA up-regulation was monitored using miRNA arrays, Northern micro-dot blots and RT-PCR. Selective NF-кB translocation and DNA binding inhibitors, including the chelator and anti-oxidant pyrollidine dithiocarbamate (PDTC) and the polyphenolic resveratrol analog CAY10512 (trans-3,5,4'-trihydroxystilbene), indicated the NF-кB sensitivity of several brain miRNAs, including miRNA-9, miRNA-125b and miRNA-146a. The inducible miRNA-125b and miRNA-146a, and their verified mRNA targets, including 15-lipoxygenase (15-LOX), synapsin-2 (SYN-2), complement factor H (CFH) and tetraspanin-12 (TSPAN12), suggests complex and highly interactive roles for NF-кB, miRNA-125b and miRNA-146a. These data further indicate that just two NF-кB-mediated miRNAs have tremendous potential to contribute to the regulation of neurotrophic support, synaptogenesis, neuroinflammation, innate immune signaling and amyloidogenesis in stressed primary neural cells of the human brain.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / genetics
  • Amyloid / physiology
  • Brain / cytology*
  • Brain / pathology
  • Brain / physiology*
  • Coculture Techniques
  • Humans
  • Immunity, Innate / genetics
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • MicroRNAs / physiology*
  • NF-kappa B / genetics*
  • NF-kappa B / physiology
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / physiology
  • Neuroglia / pathology
  • Neuroglia / physiology
  • Neurons / pathology
  • Neurons / physiology
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Synapses / genetics


  • Amyloid
  • MicroRNAs
  • NF-kappa B
  • Nerve Growth Factors