Remyelination in multiple sclerosis
(MS) is often incomplete. In experimental models, oligodendrocyte
progenitor cells (OPCs) rather than previously myelinating
oligodendrocytes (OLs) are responsible for remyelination. This study
compares the relative susceptibility of adult human OPCs and mature OLs
to injury in actively demyelinating MS lesions and under in vitro stress
conditions.
In all lesions (n = 20), the relative number of mature OLs
(Olig2 weak/NogoA positive) was reduced compared to control white matter
(mean 38 ± 4% of control value). In 11 cases, relative OPC numbers
(Olig2 strong; NogoA negative) were also decreased; in eight of these,
the percentage reduction was greater for OPCs than for mature OLs. In
the other nine samples, relative OPC numbers were greater than control
white matter, indicating ongoing OPC migration and/or proliferation.
Analysis of co-cultures with rat dorsal root ganglia neurons confirmed
that OPCs were more capable of contacting and ensheathing axons than
mature OLs. In isolated culture under stress conditions (withdrawal of
serum/glucose and/or antioxidants), OPCs showed increased cell death and
reduced process extension compared to mature OLs. Under all culture
conditions, OPCs up-regulated expression of genes in the extrinsic
proapoptotic pathway, and had increased susceptibility to tumor necrosis
factor-induced cell death as compared to OLs. Our data suggest that
susceptibility of OPCs to injury within the MS lesion environment
contributes to the limited remyelination in MS.
This study is self explanatory.