title: Microglial cystatin F expression is a sensitive indicator for ongoing demyelination with concurrent remyelination.
abstract: Demyelination coincides with numerous changes of gene expression in the central nervous system (CNS). Cystatin F, which is a papain-like lysosomal cysteine proteinase inhibitor that is normally expressed by immune cells and not in the brain, is massively induced in the CNS during acute demyelination. We found that microglia, which are monocyte/macrophage-lineage cells in the CNS, express cystatin F only during demyelination. By using several demyelinating animal models and the spinal cord tissues from multiple sclerosis (MS) patients, we examined spatiotemporal expression pattern of cystatin F by in situ hybridization and immunohistochemistry. We found that the timing of cystatin F induction matches with ongoing demyelination, and the places with cystatin F expression overlapped with the remyelinating area. Most interestingly, cystatin F induction ceased in chronic demyelination, in which remyelinating ability was lost. These findings demonstrate that the expression of cystatin F indicates the occurrence of ongoing demyelination/remyelination and the absence of cystatin F expression indicates the cessation of remyelination in the demyelinating area.
authors.affiliation: Department of Anatomy, Dalian Medical University, Dalian, Liaoning, China.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Ma
authors.forename: Kenji F
authors.initials: KF
authors.lastname: Tanaka
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shimizu
authors.forename: Claude C A
authors.initials: CC
authors.lastname: Bernard
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Kakita
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Takahashi
authors.forename: Steven E
authors.initials: SE
authors.lastname: Pfeiffer
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ikenaka
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000172:deficiency / Q000378:metabolism; D002478:Cells, Cultured; D002908:Chronic Disease; D015891:Cystatins / Q000096:biosynthesis* / Q000172:deficiency / Q000378:metabolism; D020278:Demyelinating Autoimmune Diseases, CNS / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000473:pathology; D009416:Nerve Regeneration / Q000235:genetics; D020127:Recovery of Function / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C116891:CST7 protein, human; D015891:Cystatins; C550521:cystatin F, mouse