Aktuelle Neurologie 2007; 34 - P725
DOI: 10.1055/s-2007-987995

p75NTR-knockout mice feature increased axonal vulnerability in experimental autoimmune encephalomyelitis

S Nessler 1, C Stadelmann-Nessler 1, A Bittner 1, W Jäger 1, WH Oertel 1, N Sommer 1, C Möller 1, B Hemmer 1
  • 1Düsseldorf, Göttingen, Marburg

Close interactions between the immune and the nervous system have been proposed after the discovery that immune cells produce and secrete neurotrophins and express their receptors. In multiple sclerosis (MS), the prototypic inflammatory demyelinating disease of the central nervous system, immunoreactivity for neurotrophins such as BDNF was demonstrated in lesion infiltrating immune cells. Among other neurotrophin receptors, the p75 neurotrophin receptor (p75NTR) seems to be expressed on oligodendrocyte precursors, oligodendrocytes, macrophages and microglia cells in MS lesions. In this study we addressed the significance of the p75NTR receptor system in experimental autoimmune encephalomyelitis (EAE), the animal model of MS. We induced EAE by the adoptive transfer of a MOG35–55 specific wild type T cell clone into p75NTR-/- and wild type animals. We found that p75NTR deficient animals developed adoptive transfer EAE with similar kinetics and maximum disease scores. Cellular infiltrates in early EAE were similar between the groups. However, EAE severity significantly diverged in chronic disease stages when p75NTR deficient animals suffered from more severe disease due to more axonal damage and loss. P75NTR deficient animals did not differ in the extent of demyelination, oligodendrocyte density or remyelination. Furthermore, no differential expression of GAP-43 positive axonal structures was observed in the lesions of wild type and knockout animals, suggesting that axonal regeneration is comparable. In summary, our in vivo results suggest that the p75NTR receptor has axonoprotective effects in inflammatory disease conditions.