GFAP-positive and myelin marker-positive glia in normal and pathologic environments

Abstract

The data herein demonstrate that in addition to the well-characterized myelin marker-positive, glial fibrillary acidic protein (GFAP)-negative, membrane sheet-bearing oligodendrocytes, another type of myelin marker-positive, process-bearing glia exists in normal and pathologic conditions. This second type of myelin marker-positive glia expresses GFAP, and therefore these cells have been referred to as mixed phenotype glia. Although mixed phenotype glia have been documented previously, their identity and function have remained a mystery. The goal of this immunocytochemical study was to further characterize these cells. Using the MBPlacZ transgenic mouse in which beta-galactosidase is under the control of the myelin basic protein (MBP) gene promoter, GFAP-positive/beta-galactosidase-positive and myelin/oligodendrocyte-specific protein (MOSP)-positive/beta-galactosidase-positive cells were detected in subcortical white matter and in perivascular locations within cerebral white and gray matter. In cultures prepared from highly enriched myelin marker-positive immature glia, mixed phenotype glia were detected that were GFAP-positive and either MOSP-, MBP-, O1-, and O4-positive. The expression of multiple myelin markers by mixed phenotype glia may suggest that these cells are of oligodendrocyte origin. Increased numbers of MOSP-positive/GFAP-positive mixed phenotype glia were detected in sections from adult hypomyelinated brain from shiverer, quaking, and PKU mice compared to myelinated control adult mouse brain. Similarly, cultures from control brain exposed to elevated pH for 2-3 weeks showed dramatically increased numbers of mixed phenotype glia (80%) compared to control (<10%). Increased numbers of mixed phenotype glia also were detected in shiverer cultures (40%). Since increases in the number of mixed phenotype glia occur in shiverer, quaking, and PKU mouse brain, these data suggest that mixed phenotype glia contribute to gliosis in pathologic white matter.

HMG‐CoA reductase inhibitor augments survival and differentiation of oligodendrocyte progenitors in animal model of multiple sclerosis

“…Consistent with this, the observed increase in expression of neurotrophic factors that occurs parallel to the decrease in GFAP expression in the spinal cord of LOV-treated EAE animals and treated activated mixed glial cells is suggestive of a pro-remyelinating environment induced by LOV. In agreement with these findings, reactive gliosis has been shown to be associated with hypomyelination due to the absence of MBP expressing oligodendrocytes and an increase in GFAP expressing glial cells in the white matter of the shiverer, quaking, and phenylketonuric mice brain (40). The observed increase in secretion of neurotrophic factors by LOV-treated activated glial cells indicates that LOV attenuates reactive gliosis and thereby increases the secretion of neurotrophic factors to generate a pro-remyelinating environment in the CNS.…”

Proteome modifications of the medicinal leech nervous system under bacterial challenge

“…The observation that representatives of two types of cytoskeletal filaments are modulated suggests that significant cytoskeletal rearrangements occur in one or several cell type(s) within the leech CNS as soon as after 1 h of immune challenge, and all along the first 24 h. The modulation of a tropomyosin, a protein associated with and regulating the stability of actin microfilaments [30,37], suggests that, following the exposure to a septic challenge, microfilaments undergo destabilization or stabilization all along the time course, thus facilitating or inhibiting cytoskeletal rearrangements. Although intermediate filament components are very diversified in their amino acid sequences, most of them are considered as good markers of glial cell proliferation, as GFAP is for vertebrate astrocytes [38][39][40]. Gliarin could thus be a new marker of proliferation and maturation of leech glial cells and its upregulation could reflect a glial activation in response to the immune challenge.…”

Decreased GFAP‐mRNA expression in spinal cord of cobalamin‐deficient rats

“…They all seem to be characteristic of experimental SCD, because they are corrected by post-operative Cbl replacement treatment (5,15). Parenthetically, a second type of GFAP-positive and myelin marker-positive glia has been tentatively identified as a nonmyelinating oligodendrocyte (31), and so it is conceivable that Cbl deficiency may also affect this type of glial cell.…”