Oligodendrocyte progenitor cells: from experimental remyelination to multiple sclerosis

Alison Jennings

    Research output: ThesisDoctoral Thesis

    497 Downloads (Pure)

    Abstract

    In experimental models of demyelination such as cat optic nerve injected with antibody to galactocerebroside, stepwise and ultimately full repair occurs, starting with recruitment of oligodendrocyte progenitor cells (OP) from surrounding tissue and culminating in remyelination by young competent oligodendrocytes. Endogenous repair of demyelination can also occur in the adult human central nervous system, as evidenced by remyelinated shadow plaques in MS, but ultimately fails in this disease, leading to areas of chronic demyelination where surviving axons are both dysfunctional in terms of conduction and vulnerable to ongoing damage. In order to meaningfully investigate this failure of remyelination in the human situation, an essential prerequisite is to be able to reliably identify the neuroglial cells, and in particular, oligodendrocyte lineage cells, involved in the repair pathway in situ in post mortem tissue. While some marker antigens have been shown to remain demonstrable despite autolytic change and through differing fixation levels, others are far more sensitive and only reliable in freshly obtained tissue with light fixation. For instance, the surface antigens NG2 and PDGFαR, which have been widely used in experimental studies as a marker for OP both in vivo and in vitro, have been shown to be adversely affected by both fixation and autolysis. To this end, the cat optic nerve demyelination model, in which the reparative oligodendrocyte lineage stages have been antigenically defined, was extended to normal optic nerve including lightly fixed tissue. Here, NG2, PDGFαR and the oligodendrocyte lineage transcription factors Olig1 and Olig2 were able to be demonstrated and then correlated with the existing antigenic phenotypes. Subsequently, normal human optic nerve, optimised for both morphological preservation and antigen retention, was used to develop an in vivo staining profile for all neuroglia including OP, that was then applied to conventionally prepared, normal and MS tissue. It was found that, with careful attention to technical parameters such as post mortem interval and details of fixation, OP and other stages of the remyelinating oligodendrocyte lineage could be identified in such material, resulting in meaningful insight into the repair status of the three MS samples studied.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Publication statusUnpublished - 2007

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