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Maturation‐dependent apoptotic cell death of oligodendrocytes in myelin‐deficient rats
Author(s) -
Grinspan Judith B.,
Coulalaglou Markella,
Beesley Jacqueline S.,
Carpio David F.,
Scherer Steven S.
Publication year - 1998
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/(sici)1097-4547(19981201)54:5<623::aid-jnr7>3.0.co;2-r
Subject(s) - oligodendrocyte , myelin , biology , programmed cell death , tunel assay , terminal deoxynucleotidyl transferase , microbiology and biotechnology , myelin proteolipid protein , apoptosis , myelin basic protein , chondroitin sulfate proteoglycan , myelin associated glycoprotein , central nervous system , proteoglycan , neuroscience , biochemistry , extracellular matrix
Mutations in the proteolipid protein gene ( PLP/plp ), which encodes the major intrinsic membrane protein in central nervous system (CNS) myelin, cause inherited dysmyelination in mammals. One of these mutants, the myelin‐deficient ( md) rat, has severe dysmyelination that is associated with oligodendrocyte cell death. Using the terminal deoxynucleotidyl transferase (TdT)‐mediated dUTP‐biotin nick end‐labeling (TUNEL) assay, which labels apoptotic cells, we find that cell death is increased in multiple white matter tracts of md rats. The tracts that myelinate the earliest show the earliest increase in cell death, and cell death persists for at least 22 days, the lifespan of these mutant animals. In all tracts, and at all developmental ages examined, apoptotic cells expressed the markers of mature oligodendrocytes, such as myelin basic protein, myelin‐associated glycoprotein, and the Rip antigen, but not chondroitin sulfate proteoglycan, a marker of oligodendrocyte precursors. Mature oligodendrocytes fail to accumulate in md brain because they die before they fully mature. J. Neurosci. Res. 54:623–634, 1998. © 1998 Wiley‐Liss, Inc.