Oligodendroglia are particularly vulnerable to oxidative damage after neurotrauma in vivo

Marcus K. Giacci, Carole A. Bartlett, Nicole M. Smith, K. Swaminathan Iyer, Lillian M. Toomey, Haibo Jiang, Paul Guagliardo, Matt R. Kilburn, Melinda Fitzgerald

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Loss of function following injury to the CNS is worsened by secondary degeneration of neurons and glia surrounding the injury and is initiated by oxidative damage. However, it is not yet known which cellular populations and structures are most vulnerable to oxidative damage in vivo. Using Nanoscale secondary ion mass spectrometry (NanoSIMS), oxidative damage was semiquantified within cellular subpopulations and structures of optic nerve vulnerable to secondary degeneration, following a partial transection of the optic nerve in adult female PVG rats. Simultaneous assessment of cellular subpopulations and structures revealed oligodendroglia as the most vulnerable to DNA oxidation following injury. 5-Ethynyl-2′-deoxyuridine (EdU) was used to label cells that proliferated in the first 3 d after injury. Injury led to increases in DNA, protein, and lipid damage in oligodendrocyte progenitor cells and mature oligodendrocytes at 3 d, regardless of proliferative state, associated with a decline in the numbers of oligodendrocyte progenitor cells at 7 d. O4+ preoligoden-drocytes also exhibited increased lipid peroxidation. Interestingly, EdU+ mature oligodendrocytes derived after injury demonstrated increased early susceptibility to DNA damage and lipid peroxidation. However, EdU- mature oligodendrocytes with high 8-hydro-xyguanosine immunoreactivity were more likely to be caspase3+. By day 28, newly derived mature oligodendrocytes had significantly reduced myelin regulatory factor gene mRNA, indicating that the myelination potential of these cells may be reduced. The proportion of caspase3+; oligodendrocytes remained higher in EdU- cells. Innovative use of NanoSIMS together with traditional immunohistochem-istry and in situ hybridization have enabled the first demonstration of subpopulation specific oligodendroglial vulnerability to oxidative damage, due to secondary degeneration in vivo.

Original languageEnglish
Pages (from-to)6491-6504
Number of pages14
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume38
Issue number29
DOIs
Publication statusPublished - 18 Jul 2018

Fingerprint

Oligodendroglia
Wounds and Injuries
Cellular Structures
Secondary Ion Mass Spectrometry
Lipid Peroxidation
Stem Cells
Optic Nerve Injuries
Nerve Degeneration
DNA
Regulator Genes
Optic Nerve
Myelin Sheath
Neuroglia
DNA Damage
In Situ Hybridization
Lipids
Messenger RNA
5-ethynyl-2'-deoxyuridine
Population

Cite this

@article{04ed734c0b17415992d493686abbbfea,
title = "Oligodendroglia are particularly vulnerable to oxidative damage after neurotrauma in vivo",
abstract = "Loss of function following injury to the CNS is worsened by secondary degeneration of neurons and glia surrounding the injury and is initiated by oxidative damage. However, it is not yet known which cellular populations and structures are most vulnerable to oxidative damage in vivo. Using Nanoscale secondary ion mass spectrometry (NanoSIMS), oxidative damage was semiquantified within cellular subpopulations and structures of optic nerve vulnerable to secondary degeneration, following a partial transection of the optic nerve in adult female PVG rats. Simultaneous assessment of cellular subpopulations and structures revealed oligodendroglia as the most vulnerable to DNA oxidation following injury. 5-Ethynyl-2′-deoxyuridine (EdU) was used to label cells that proliferated in the first 3 d after injury. Injury led to increases in DNA, protein, and lipid damage in oligodendrocyte progenitor cells and mature oligodendrocytes at 3 d, regardless of proliferative state, associated with a decline in the numbers of oligodendrocyte progenitor cells at 7 d. O4+ preoligoden-drocytes also exhibited increased lipid peroxidation. Interestingly, EdU+ mature oligodendrocytes derived after injury demonstrated increased early susceptibility to DNA damage and lipid peroxidation. However, EdU- mature oligodendrocytes with high 8-hydro-xyguanosine immunoreactivity were more likely to be caspase3+. By day 28, newly derived mature oligodendrocytes had significantly reduced myelin regulatory factor gene mRNA, indicating that the myelination potential of these cells may be reduced. The proportion of caspase3+; oligodendrocytes remained higher in EdU- cells. Innovative use of NanoSIMS together with traditional immunohistochem-istry and in situ hybridization have enabled the first demonstration of subpopulation specific oligodendroglial vulnerability to oxidative damage, due to secondary degeneration in vivo.",
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Oligodendroglia are particularly vulnerable to oxidative damage after neurotrauma in vivo. / Giacci, Marcus K.; Bartlett, Carole A.; Smith, Nicole M.; Iyer, K. Swaminathan; Toomey, Lillian M.; Jiang, Haibo; Guagliardo, Paul; Kilburn, Matt R.; Fitzgerald, Melinda.

In: The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 38, No. 29, 18.07.2018, p. 6491-6504.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Oligodendroglia are particularly vulnerable to oxidative damage after neurotrauma in vivo

AU - Giacci, Marcus K.

AU - Bartlett, Carole A.

AU - Smith, Nicole M.

AU - Iyer, K. Swaminathan

AU - Toomey, Lillian M.

AU - Jiang, Haibo

AU - Guagliardo, Paul

AU - Kilburn, Matt R.

AU - Fitzgerald, Melinda

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PY - 2018/7/18

Y1 - 2018/7/18

N2 - Loss of function following injury to the CNS is worsened by secondary degeneration of neurons and glia surrounding the injury and is initiated by oxidative damage. However, it is not yet known which cellular populations and structures are most vulnerable to oxidative damage in vivo. Using Nanoscale secondary ion mass spectrometry (NanoSIMS), oxidative damage was semiquantified within cellular subpopulations and structures of optic nerve vulnerable to secondary degeneration, following a partial transection of the optic nerve in adult female PVG rats. Simultaneous assessment of cellular subpopulations and structures revealed oligodendroglia as the most vulnerable to DNA oxidation following injury. 5-Ethynyl-2′-deoxyuridine (EdU) was used to label cells that proliferated in the first 3 d after injury. Injury led to increases in DNA, protein, and lipid damage in oligodendrocyte progenitor cells and mature oligodendrocytes at 3 d, regardless of proliferative state, associated with a decline in the numbers of oligodendrocyte progenitor cells at 7 d. O4+ preoligoden-drocytes also exhibited increased lipid peroxidation. Interestingly, EdU+ mature oligodendrocytes derived after injury demonstrated increased early susceptibility to DNA damage and lipid peroxidation. However, EdU- mature oligodendrocytes with high 8-hydro-xyguanosine immunoreactivity were more likely to be caspase3+. By day 28, newly derived mature oligodendrocytes had significantly reduced myelin regulatory factor gene mRNA, indicating that the myelination potential of these cells may be reduced. The proportion of caspase3+; oligodendrocytes remained higher in EdU- cells. Innovative use of NanoSIMS together with traditional immunohistochem-istry and in situ hybridization have enabled the first demonstration of subpopulation specific oligodendroglial vulnerability to oxidative damage, due to secondary degeneration in vivo.

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KW - NanoSIMS

KW - Oligodendrocyte precursor cell

KW - Oligodendroglia

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DO - 10.1523/JNEUROSCI.1898-17.2018

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