Sex hormone-dependent attenuation of EAE in a transgenic mouse with astrocytic expression of the RNA regulator HuR

J Neuroimmunol. 2012 May 15;246(1-2):34-7. doi: 10.1016/j.jneuroim.2012.02.014. Epub 2012 Mar 22.

Abstract

In experimental autoimmune encephalomyelitis (EAE) and other neurodegenerative diseases, astrocytes play an important role in promoting or attenuating the inflammatory response through induction of different cytokines and growth factors. HuR plays a major role in regulating many of these factors by modulating RNA stability and translational efficiency. Here, we engineered transgenic mice to express HuR in astrocytes using the human glial fibrillary acidic protein promoter and found that female transgenic mice had significantly less clinical disability and histopathological changes in the spinal cord. Ovariectomy prior to EAE induction abrogated the protective effect. Our findings support a role for the astrocyte and posttranscriptional regulation in hormonally-mediated attenuation of EAE.

Publication types

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

MeSH terms

  • Animals
  • Astrocytes / immunology
  • Astrocytes / metabolism*
  • Astrocytes / pathology
  • ELAV Proteins / biosynthesis*
  • ELAV Proteins / genetics*
  • ELAV Proteins / physiology
  • Encephalomyelitis, Autoimmune, Experimental / genetics*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Estradiol Congeners / physiology*
  • Female
  • Gene Expression Regulation / immunology*
  • Humans
  • Mice
  • Mice, Transgenic
  • Spinal Cord / immunology
  • Spinal Cord / metabolism
  • Spinal Cord / pathology

Substances

  • ELAV Proteins
  • Estradiol Congeners