Differential expression of protease M/neurosin in oligodendrocytes and their progenitors in an animal model of multiple sclerosis.
To determine the possible involvement of protease M/neurosin in demyelinating diseases of the CNS, we examined its expression in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), a recognized animal model of multiple sclerosis (MS). In situ hybridization, immunohistochemistry and quantitative real-time polymerase chain reaction (PCR) demonstrated that EAE caused an increase in the expression of protease M/neurosin mRNA and its protein product throughout the white and gray matter surrounding demyelinating lesions. Combined in situ hybridization and immunohistochemistry demonstrated that most of the cells expressing protease M/neurosin mRNA within control spinal cord showed immunoreactivity for CNPase or NG2, cell-specific markers for oligodendrocytes and their progenitors, respectively. In the spinal cord from mice with EAE, the expression of protease M/neurosin mRNA in CNPase-positive cells appeared to be increased while double-labeled cells positive for protease M/neurosin mRNA and NG2 were rarely found in areas associated with demyelinating lesions. Although a prominent accumulation of inflammatory cells including T-cells was observed in the vicinity of demyelinated lesions, these cells were not associated with protease M/neurosin mRNA expression. The levels of protease M/neurosin mRNA expression were unchanged in the spleen and even decreased in the thymus during the course of EAE. These observations suggest that the differential expression of protease M/neurosin in mature oligodendrocytes and their progenitors is involved in the pathogenesis of MS and EAE.
Terayama
Ryuji
R
Department of Anatomy, Asahikawa Medical College, 2-1-1-1 Midorigaoka-Higashi, Asahikawa 078-8510, Japan. rjt001@asahikawa-med.ac.jp
Bando
Yoshio
Y
Jiang
Ying-Ping
YP
Mitrovic
Branka
B
Yoshida
Shigetaka
S
D000818:Animals; D002490:Central Nervous System / Q000201:enzymology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000201:enzymology* / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007610:Kallikreins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000201:enzymology* / Q000473:pathology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000201:enzymology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D007610:Kallikreins; C491223:Prss18 protein, mouse