eISSN: 1509-572x
ISSN: 1641-4640
Folia Neuropathologica
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SCImago Journal & Country Rank
1/2019
vol. 57
 
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abstract:
Original paper

Disturbed maturation of oligodendrocyte progenitors in lipopolysaccharide-induced hypomyelination in cultured forebrain slices of neonatal rats

Jong-Wan Kim, Kun Song Lee, Young Pyo Chang

Folia Neuropathol 2019; 57 (1): 24-35
Online publish date: 2019/03/29
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Introduction
This study was performed to determine whether the disturbed maturation of oligodendrocyte (OL) progenitors might be related to lipopolysaccharide (LPS)-induced hypomyelination.

Material and methods
We created organotypic cultures of forebrain slices from neonatal rats and explored the morphological changes of glial cells expressing tumour necrosis factor  (TNF-) following LPS exposure.

Results
We observed marked activation of glial fibrillary acidic protein-positive astrocytes and OX42-positive microglia co-labelled with TNF- four days following LPS exposure. Our results further demonstrated a reduced expression of O4-positive and O1-positive OL progenitors; moreover, we found that their morphologies were suggestive of degeneration (e.g., scanty, rounded bodies with short, fragmented processes and/or cytoplasmic condensation). At seven days following LPS exposure, astrocytes and microglia were still co-labelled for TNF-; however, the expression of O4-positive and O1-positive cells somewhat increased compared to the number observed at 4 days; despite remaining undifferentiated and exhibiting immature morphologies, the cells were likely indicative of regeneration. In contrast, O4-positive and O1-positive cells in controls were well-differentiated, displaying round, thick cell bodies and long, branching processes.

Conclusions
In conclusion, maturation arrest and/or under-differentiation of OL progenitors commonly occur during regeneration: they may underlie the degeneration and consequent hypomyelination occurring late after injury, or apoptosis during the acute stage post-injury. Microglia and astrocytes expressing TNF- may also contribute to later myelination failure.

keywords:

maturation arrest, oligodendrocyte progenitor, hypomyelination, glial cells, lipopolysaccharide, proinflammatory cytokine

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