In vitro analysis of the oligodendrocyte lineage in mice during demyelination and remyelination
- National Institute of Neurological Disorders and Stroke, Bethesda, MD (USA)
A demyelinating disease induced in C57B1/6N mice by intracranial injection of a coronavirus (murine hepatitis virus strain A59) is followed by functional recovery and efficient CNS myelin repair. To study the biological properties of the cells involved in this repair process, glial cells were isolated and cultured from spinal cords of these young adult mice during demyelination and remyelination. Using three-color immunofluorescence combined with (3H)thymidine autoradiography, we have analyzed the antigenic phenotype and mitotic potential of individual glial cells. We identified oligodendrocytes with an antibody to galactocerebroside, astrocytes with an antibody to glial fibrillary acidic protein, and oligodendrocyte-type 2 astrocyte (O-2A) progenitor cells with the O4 antibody. Cultures from demyelinated tissue differed in several ways from those of age-matched controls: first, the total number of O-2A lineage cells was strikingly increased; second, the O-2A population consisted of a higher proportion of O4-positive astrocytes and cells of mixed oligodendrocyte-astrocyte phenotype; and third, all the cell types within the O-2A lineage showed enhanced proliferation. This proliferation was not further enhanced by adding PDGF, basic fibroblast growth factor (bFGF), or insulin-like growth factor I (IGF-I) to the defined medium. However, bFGF and IGF-I seemed to influence the fate of O-2A lineage cells in cultures of demyelinated tissue. Basic FGF decreased the percentage of cells expressing galactocerebroside. In contrast, IGF-I increased the relative proportion of oligodendrocytes. Thus, O-2A lineage cells from adult mice display greater phenotypic plasticity and enhanced mitotic potential in response to an episode of demyelination. These properties may be linked to the efficient remyelination achieved in this demyelinating disease.
- OSTI ID:
- 6367157
- Journal Information:
- Journal of Cell Biology, Journal Name: Journal of Cell Biology Journal Issue: 3 Vol. 111; ISSN 0021-9525
- Publisher:
- Rockefeller University Press
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMALS
AUTORADIOGRAPHY
AZINES
BIOLOGICAL RECOVERY
CELL DIFFERENTIATION
CENTRAL NERVOUS SYSTEM
DISEASES
GROWTH FACTORS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
IN VITRO
INFECTIOUS DISEASES
MAMMALS
MICE
MITOGENS
NERVE CELLS
NERVOUS SYSTEM
NUCLEOSIDES
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PATHOGENESIS
PHENOTYPE
PROTEINS
PYRIMIDINES
RECOVERY
RIBOSIDES
RODENTS
SOMATIC CELLS
THYMIDINE
TRITIUM COMPOUNDS
VERTEBRATES
VIRAL DISEASES