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Olig2‐lineage cells preferentially differentiate into oligodendrocytes but their processes degenerate at the chronic demyelinating stage of proteolipid protein‐overexpressing mouse
Author(s) -
Shimizu Takahiro,
Tanaka Kenji F.,
Takebayashi Hirohide,
Higashi Mikito,
Wisesmith Wilaiwan,
Ono Katsuhiko,
Hitoshi Seiji,
Ikenaka Kazuhiro
Publication year - 2013
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.23153
Subject(s) - olig2 , oligodendrocyte , myelin , lineage markers , proteolipid protein 1 , biology , demyelinating disease , myelin basic protein , remyelination , microbiology and biotechnology , neural stem cell , stem cell , immunology , pathology , neuroscience , central nervous system , progenitor cell , multiple sclerosis , medicine
In chronic demyelinating lesions of the central nervous system, insufficient generation of oligodendrocytes (OLs) is not due to a lack of oligodendrocyte precursor cells (OPCs), because the accumulation of OPCs and premyelinating OLs can be observed within these lesions. Here we sought to identify the basis for the failure of OLs to achieve terminal differentiation in chronic demyelinating lesions through the utilization of plp1 ‐overexpressing ( Plp tg /− ) mice. These mice are characterized by progressive demyelination in young adults and chronic demyelinating lesions at more mature stages. We show that neural stem cells, which are the precursors of OL‐lineage cells, are present in the Plp tg /− mouse brain and that their multipotentiality and ability to self‐renew are comparable to those of wild‐type adults in culture. Lineage‐tracing experiments using a transgenic mouse line, in which an inducible Cre recombinase is knocked in at the Olig2 locus, revealed that Olig2‐lineage cells preferentially differentiated into OPCs and premyelinating OLs, but not into astrocytes, in the Plp tg /− mouse brain. These Olig2‐lineage cells matured to express myelin basic protein but after that their processes degenerated in the chronic demyelinating lesions of the Plp tg /− brain. These results indicate that in chronic demyelinated lesions more OL‐lineage cells are produced as part of the repair process, but their processes degenerate after maturation. © 2012 Wiley Periodicals, Inc.