Microglial cystatin F expression is a sensitive indicator for ongoing demyelination with concurrent remyelination

Jianmei Ma, Kenji Tanaka, Takahiro Shimizu, Claude C A Bernard, Akiyoshi Kakita, Hitoshi Takahashi, Steven E. Pfeiffer, Kazuhiro Ikenaka

Research output: Contribution to journalArticle

31 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)639-649
Number of pages11
JournalJournal of Neuroscience Research
Volume89
Issue number5
DOIs
Publication statusPublished - 2011 May
Externally publishedYes

Fingerprint

Cystatins
Demyelinating Diseases
Central Nervous System
Cysteine Proteinase Inhibitors
Papain
Microglia
Multiple Sclerosis
In Situ Hybridization
Monocytes
Spinal Cord
Animal Models
Immunohistochemistry
Macrophages
Gene Expression

Keywords

  • CNS
  • Cystatin F
  • Demyelination
  • Multiple sclerosis (MS)
  • Remyelination

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Microglial cystatin F expression is a sensitive indicator for ongoing demyelination with concurrent remyelination. / Ma, Jianmei; Tanaka, Kenji; Shimizu, Takahiro; Bernard, Claude C A; Kakita, Akiyoshi; Takahashi, Hitoshi; Pfeiffer, Steven E.; Ikenaka, Kazuhiro.

In: Journal of Neuroscience Research, Vol. 89, No. 5, 05.2011, p. 639-649.

Research output: Contribution to journalArticle

Ma, Jianmei ; Tanaka, Kenji ; Shimizu, Takahiro ; Bernard, Claude C A ; Kakita, Akiyoshi ; Takahashi, Hitoshi ; Pfeiffer, Steven E. ; Ikenaka, Kazuhiro. / Microglial cystatin F expression is a sensitive indicator for ongoing demyelination with concurrent remyelination. In: Journal of Neuroscience Research. 2011 ; Vol. 89, No. 5. pp. 639-649.
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