Adjuvant-induced arthritis induces c-Fos chronically in neurons in the hippocampus

J Neuroimmunol. 2011 Jan;230(1-2):85-94. doi: 10.1016/j.jneuroim.2010.09.005. Epub 2010 Oct 15.


Chronic pain, sickness behaviors, and cognitive decline are symptoms in rheumatoid arthritis. In the adjuvant-induced arthritis Lewis rat model, we examined the dynamics of c-Fos expression in the hippocampus, a brain region important for these symptoms. Brain sections were stained for c-Fos using immunohistochemistry. c-Fos-positive nuclei were counted in CA1, CA2, CA3 and the dentate gyrus of the dorsal hippocampi from rats receiving no treatment or base-of-the-tail injections of (1 or 2) incomplete or complete Freund's adjuvant (low- or high-dose), (3), Mycobacterium butyricum cell wall suspended in saline, or (4) saline, and sacrificed 4, 14, 21, or 126days post-immunization. Disease severity was evaluated by dorsoplantar foot pad widths and X-ray analysis. We report sustained dose- and subfield-dependent c-Fos expression with arthritis, but transient expression in nonarthritic groups, suggesting long-term genomic changes in rheumatoid arthritis that may be causal for behavioral changes, adaptation to chronic pain and/or cognitive decline associated with disease.

MeSH terms

  • Animals
  • Arthritis, Experimental / metabolism*
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / physiopathology
  • Arthritis, Rheumatoid / metabolism*
  • Arthritis, Rheumatoid / physiopathology
  • Gene Expression
  • Hippocampus / metabolism*
  • Hippocampus / pathology
  • Hippocampus / physiopathology
  • Immunohistochemistry
  • Male
  • Neurons / metabolism*
  • Neurons / pathology
  • Proto-Oncogene Proteins c-fos / biosynthesis*
  • Rats
  • Rats, Inbred Lew


  • Proto-Oncogene Proteins c-fos