Involvement of neuropsin in the pathogenesis of experimental autoimmune encephalomyelitis.
Inflammation, demyelination, and axonal damage of the central nervous system (CNS) are major pathological features of multiple sclerosis (MS). Proteolytic digestion of the blood-brain barrier and myelin protein by serine proteases is known to contribute to the development and progression of MS. Neuropsin, a serine protease, has a role in neuronal plasticity, and its expression has been shown to be upregulated in response to injury to the CNS. To determine the possible involvement of neuropsin in demyelinating diseases of the CNS, we examined its expression in myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE), a recognized animal model for MS. Neuropsin mRNA expression was induced in the spinal cord white matter of mice with EAE. Combined in situ hybridization and immunohistochemistry demonstrated that most of the cells expressing neuropsin mRNA showed immunoreactivity for CNPase, a cell-specific marker for oligodendrocytes. Mice lacking neuropsin (neuropsin-/-) exhibited an altered EAE progression characterized by delayed onset and progression of clinical symptoms as compared to wild-type mice. Neuropsin-/- mice also showed attenuated demyelination and delayed oligodendroglial death early during the course of EAE. These observations suggest that neuropsin is involved in the pathogenesis of EAE mediated by demyelination and oligodendroglial death.
Terayama
Ryuji
R
Department of Anatomy, Asahikawa Medical College, Asahikawa, Japan. rjt001@asahikawa-med.ac.jp
Bando
Yoshio
Y
Yamada
Masahiro
M
Yoshida
Shigetaka
S
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000818:Animals; D003711:Demyelinating Diseases / Q000473:pathology; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007610:Kallikreins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000378:metabolism; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D005904:Glial Fibrillary Acidic Protein; C571327:Mog protein, mouse; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D007610:Kallikreins; C114664:Prss19 protein, mouse; D012697:Serine Endopeptidases