@misc{oai:ir.soken.ac.jp:00001148,
 author = {松本, 路生 and マツモト, ミチオ and MATSUMOTO, Michio},
 month = {2016-02-17, 2016-02-17},
 note = {Overexpression of the proteolipid protein (PLP) gene, which is the major component of central nervous system myelin, causes unique demyelinating disorder in mice(Plp/- mouse). In this transgenic animal model, normal-appearing myelin is formed at an early stage of their life and late-onset chronic demyelination occurs after several months. I aimed to understand the molecular mechanisms underlying this neuropathology. I first demonstrated that remyelination is severely affected in the aged Plp/- mouse. This was not caused by the deprivation of oligodendrocyte progenitors, expressing Olig1, Olig2 and Sox10, because they were present at a higher number in the central nervous system of mutant mice than in the wild type control throughout their lives. These suggested that oligodendrocyte progenitors cannot differentiate or mature due to a change in the microenvironment. I then searched for factors inhibiting oligodendrocyte development. I observed up-regulation of PSA-NCAM and cystatin C expression, both of which have been reported to be inhibitory for oligodendrocyte development and are produced by nonoligodendroglial cells. Thus I investigated the change in the number and properties of astrocytes and microglia. Glial activation was observed much earlier than the active demyelinating period. These data imply that not only cell intrinsic mechanisms but also extrinsic mechanisms contribute to the defect in re-myelination in the PLP overexpressing brain. During demyelination, resident microglial cells and astrocytes become activated, astrogliosis occurs, and these cells may change the environment to that inhibitory for oligodendrocyte differentiation/maturation., application/pdf, 総研大甲第784号},
 title = {Glial cell activation and re-expression of putative myelinating inhibitors in the brain of mouse model for demyelinating disease},
 year = {}
}