Cuprizone-induced graded oligodendrocyte vulnerability is regulated by the transcription factor DNA damage-inducible transcript 3

Glia
Felix FischbachMarkus Kipp

Abstract

Oligodendrocytes are integral to efficient neuronal signaling. Loss of myelinating oligodendrocytes is a central feature of many neurological diseases, including multiple sclerosis (MS). The results of neuropathological studies suggest that oligodendrocytes react with differing sensitivity to toxic insults, with some cells dying early during lesion development and some cells being resistant for weeks. This proposed graded vulnerability has never been demonstrated but provides an attractive window for therapeutic interventions. Furthermore, the biochemical pathways associated with graded oligodendrocyte vulnerability have not been well explored. We used immunohistochemistry and serial block-face scanning electron microscopy (3D-SEM) to show that cuprizone-induced metabolic stress results in an "out of phase" degeneration of oligodendrocytes. Although expression induction of stress response transcription factors in oligodendrocytes occurs within days, subsequent oligodendrocyte apoptosis continues for weeks. In line with the idea of an out of phase degeneration of oligodendrocytes, detailed ultrastructural reconstructions of the axon-myelin unit demonstrate demyelination of single internodes. In parallel, genome wide array analys...Continue Reading

References

Feb 1, 1981·Journal of the Neurological Sciences·W F Blakemore, J A Murray
Dec 3, 1999·Brain : a Journal of Neurology·C LucchinettiHans Lassmann
Oct 1, 2003·Molecular and Cellular Biology·Sara B CullinanJ Alan Diehl
Jul 1, 2004·The Journal of Cell Biology·Julia EdgarIan R Griffiths
Sep 22, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Laurence DeckerPatrick Charnay
Mar 18, 2008·Journal of Neuropathology and Experimental Neurology·Aoife Ní MháilleUna FitzGerald
Mar 17, 2009·Nature Neuroscience·Wensheng Lin, Brian Popko
Aug 5, 2009·The Journal of Cell Biology·Julie HollienJonathan S Weissman
Sep 12, 2009·Current Opinion in Neurobiology·Alexander Gow, Lawrence Wrabetz
Oct 27, 2009·Neurobiology of Disease·Amke HesseTanja Kuhlmann
Feb 17, 2010·Brain : a Journal of Neurology·Sara VetoZsolt Illes
Feb 24, 2010·Brain Research·Fabian BaertlingMarkus Kipp
Mar 9, 2011·Multiple Sclerosis : Clinical and Laboratory Research·Paula CunneaUna FitzGerald
Dec 20, 2011·Stroke; a Journal of Cerebral Circulation·Zhaohui HeJohn H Zhang
Feb 23, 2012·Multiple Sclerosis : Clinical and Laboratory Research·J M McMahonUna FitzGerald
May 25, 2012·Nature·Ursula FünfschillingKlaus-Armin Nave
Jan 31, 2013·Brain : a Journal of Neurology·Tobias EngelDavid C Henshall
Mar 12, 2013·Neuron·Kaylene M YoungWilliam D Richardson
Mar 25, 2014·Trends in Biochemical Sciences·M MaurelS Gerlo
Mar 25, 2014·Frontiers in Cellular Neuroscience·Viktoria GudiMartin Stangel
Apr 3, 2014·PloS One·Sung S ChoiSeung U Kim
Jun 25, 2014·Proceedings of the National Academy of Sciences of the United States of America·Nobuhiko OhnoBruce D Trapp
Sep 5, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yifeng LinWensheng Lin
Sep 6, 2014·Journal of Molecular Neuroscience : MN·Barbara KrauspeMarkus Kipp
Oct 17, 2014·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Yao Lulu XingTobias D Merson
Mar 1, 2015·The Journal of Immunology : Official Journal of the American Association of Immunologists·Tim ClarnerMarkus Kipp
Jun 5, 2015·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Edel HennessyColm Cunningham
Aug 25, 2015·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Michelle C NaughtonUna FitzGerald
Feb 14, 2016·Lancet Neurology·Sharon W Way, Brian Popko
Jun 28, 2016·Nature Reviews. Immunology·Joep GrootjansRichard S Blumberg
Sep 7, 2016·Brain Research·Katharina Marie HöflichTanja Hochstrasser

Citations

Nov 7, 2019·Cells·Stella NyamoyaMarkus Kipp
Apr 5, 2020·Cells·Jiangshan ZhanMarkus Kipp
Apr 3, 2019·Journal of Molecular Neuroscience : MN·Patrizia LeopoldMarkus Kipp
Oct 2, 2020·Cells·Sven Olaf RohrMarkus Kipp
Nov 11, 2020·Scientific Reports·Kaitlyn Koenig Thompson, Stella E Tsirka
Dec 22, 2020·Journal of Molecular Neuroscience : MN·Newshan BehrangiMarkus Kipp
Dec 10, 2019·Biochimica Et Biophysica Acta. Molecular Basis of Disease·Monica R LangleyIsobel A Scarisbrick

Related Concepts

Related Feeds

Astrocytes & Neurodegeneration

Astrocytes are important for the health and function of the central nervous system. When these cells stop functioning properly, either through gain of function or loss of homeostatic controls, neurodegenerative diseases can occur. Here is the latest research on astrocytes and neurodegeneration.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Addiction

This feed focuses mechanisms underlying addiction and addictive behaviour including heroin and opium dependence, alcohol intoxication, gambling, and tobacco addiction.