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+ preoligodendrocytes 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-hydroxyguanosine 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 immunohistochemistry and in situ hybridization have enabled the first demonstration of subpopulation specific oligodendroglial vulnerability to oxidative damage, due to secondary degeneration in vivoSIGNIFICANCE STATEMENT Injury to the CNS is characterized by oxidative damage in areas adjacent to the injury. However, the cellular subpopulations and structures most vulnerable to this damage remain to be elucidated. Here we use powerful NanoSIMS techniques to show increased oxidative damage in oligodendroglia and axons and to demonstrate that cells early in the oligodendroglial lineage are the most vulnerable to DNA oxidation. Further immunohistochemical and in situ hybridization investigation reveals that mature oligodendrocytes derived after injury are more vulnerable to oxidative damage than their counterparts existing at the time of injury and have reduced myelin regulatory factor gene mRNA, yet preexisting oligodendrocytes are more likely to die.
Pubmed ID: 29915135 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This polyclonal targets Caspase-3
View all literature mentionsThis monoclonal targets O4
View all literature mentionsThis monoclonal targets 3-Nitrotyrosine antibody [39B6]
View all literature mentionsThis polyclonal targets Human Olig2
View all literature mentionsThis polyclonal targets 4 Hydroxynonenal antibody
View all literature mentionsThis monoclonal targets Rat NG2
View all literature mentionsThis monoclonal targets 8 Hydroxyguanosine antibody [15A3]
View all literature mentionsThis monoclonal targets APC
View all literature mentionsThis polyclonal targets Myelin Basic Protein
View all literature mentionsThis polyclonal targets NG2 antibody
View all literature mentionsThis polyclonal targets Rat Caspr
View all literature mentionsThis polyclonal targets 8 Hydroxyguanosine antibody
View all literature mentionsThis polyclonal targets 4 Hydroxynonenal antibody
View all literature mentionsThis monoclonal targets 3-Nitrotyrosine antibody [39B6]
View all literature mentionsThis polyclonal targets Myelin Basic Protein
View all literature mentionsThis polyclonal targets Rat Caspr
View all literature mentionsThis polyclonal targets 8 Hydroxyguanosine antibody
View all literature mentionsThis polyclonal targets NG2 antibody
View all literature mentionsThis polyclonal targets Caspase-3
View all literature mentionsThis monoclonal targets APC
View all literature mentionsThis monoclonal targets Rat NG2
View all literature mentionsThis polyclonal targets Human Olig2
View all literature mentionsThis monoclonal targets 8 Hydroxyguanosine antibody [15A3]
View all literature mentionsThis monoclonal targets O4
View all literature mentionsThis polyclonal targets 8 Hydroxyguanosine antibody
View all literature mentionsThis monoclonal targets APC
View all literature mentionsThis polyclonal targets NG2 antibody
View all literature mentionsThis polyclonal targets Myelin Basic Protein
View all literature mentions