Quantification of oligodendrocyte progenitor cells in human and cat optic nerve: Implications for endogenous repair in multiple sclerosis

Abstract

In multiple sclerosis (MS), one strategy to reduce disability is enhancement of endogenous repair by remyelinating oligodendrocytes derived from oligodendrocyte progenitor cells (OP). An important prerequisite is determining the abundance of OP relative to oligodendrocytes in normal human central nervous system (CNS), which, in turn, requires reliable OP identification. To achieve this, cat and human optic nerves (ON) were subjected to varied preparation protocols, and the resultant neuroglial staining profiles correlated to generate an antigenic phenotype for OP applicable to human autopsy specimens. OP, interchangeably called NG2cells due to universal NG2 expression, were shown to comprise a separate class of neuroglial cells, related to oligodendrocytes by expression of the oligodendrocyte lineage transcription factors, Olig1 and Olig2. Despite their morphological complexity, including contact with axons and other neuroglia, NG2cells all appear capable of responding as OP to counter local oligodendrocyte loss. However, quantification revealed that NG2cells comprised less than 5% of the neuroglia and had a ratio to oligodendrocytes of about 1:10, not only in human and cat ON but also in white and gray-matter regions of cat spinal cord. The finding that NG2cells are not abundant, particularly relative to oligodendrocytes, may have implications for efforts to enhance endogenous repair in MS.

Multicolor analysis of oligodendrocyte morphology, interactions, and development with Brainbow

“…E). In agreement with previous studies (Jennings and Carroll, ; Ligon et al, ; Payne et al, ), we found that in the optic nerve, NG2+/Olig2+ cells only accounted for about 10% of the Olig2+ cell population (541 Olig2+ cells from two optic nerves). Interestingly, in adult CAGbow optic nerves, RFP cells were always negative for NG2 (Fig.…”

Identification and Quantification of Oligodendrocyte Precursor Cells in Multiple System Atrophy, Progressive Supranuclear Palsy and Parkinson's Disease

“…NG2 cells were also positive for the oligodendrocyte lineage nuclear transcription factor, Olig2, and negative for astrocytic and microglial markers, confirming the presence of OPCs. Consistent with a recent report , Olig2 immunoreactivity was increased in NG2‐positive cells compared with NG2‐negative/Olig2‐positive cells, the latter is thought to represent mature oligodendrocytes. This raises the possibility that the intensity of Olig2 labeling could be used in the future to distinguish between OPCs and mature oligodendrocytes, especially given that Olig2 IHC is reliable in brain‐banked FFPE tissues .…”

“…To confirm the presence of NG2-positive cells, DI labeling using NG2 and other cell-specific markers, such as Olig2 (oligodendroglial lineage), GFAP (astrocytes) and Iba-1 (microglia), was performed in the frontal region and cerebellum of PD and normal controls ( Figure 1). As previously reported (9,25), NG2positive cells with a stellate and branched morphology were also positive for the oligodendrocyte lineage marker, Olig2, but were negative for astrocytic and microglial markers. Olig2 immunoreactivity in NG2-positive cells had a nuclear localization and was consistently more intense compared with nuclear-Olig2 in NG2negative cells, the latter of which is likely to represent mature oligodendrocytes.…”

Roles of NG2 glial cells in diseases of the central nervous system

“…Acute demyelination is repaired efficiently, while remyelination fails in chronic lesions [37] . This may result from an insufficiency or the depletion of NG2 cells over time, since quantitative analysis shows that NG2 cells only account for less than 5% of the total number of glial cells, while the number of oligodendrocytes is approximately 10-fold higher [38] .…”