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The Effects of Cuprizone on Murine Subventricular Zone-Derived Neural Stem Cells and Progenitor Cells Grown as Neurospheres

Despite the extensive use of the cuprizone (CPZ) demyelination animal model, there is little evidence regarding the effects of CPZ on a cellular level. Initial studies have suggested that oligodendrocytes (OL) are the main cell targets for CPZ toxicity. However, recent data have revealed additional...

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Published in:Molecular neurobiology 2023-03, Vol.60 (3), p.1195-1213
Main Authors: Molinari, Yamila Azul, Byrne, Agustín Jesús, Pérez, María Julia, Silvestroff, Lucas, Franco, Paula Gabriela
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description Despite the extensive use of the cuprizone (CPZ) demyelination animal model, there is little evidence regarding the effects of CPZ on a cellular level. Initial studies have suggested that oligodendrocytes (OL) are the main cell targets for CPZ toxicity. However, recent data have revealed additional effects on neural stem cells and progenitor cells (NSC/NPC), which constitute a reservoir for OL regeneration during brain remyelination. We cultured NSC/NPC as neurospheres to investigate CPZ effects on cell mechanisms which are thought to be involved in demyelination and remyelination processes in vivo. Proliferating NSC/NPC cultures exposed to CPZ showed overproduction of intracellular reactive oxygen species and increased progenitor migration at the expense of a significant inhibition of cell proliferation. Although NSC/NPC survival was not affected by CPZ in proliferative conditions, we found that CPZ-treated cultures undergoing cell differentiation were more prone to cell death than controls. The commitment and cell differentiation towards neural lineages did not seem to be affected by CPZ, as shown by the conserved proportions of OL, astrocytes, and neurons. Nevertheless, when CPZ treatment was performed after cell differentiation, we detected a significant reduction in the number and the morphological complexity of OL, astrogliosis, and neuronal damage. We conclude that, in addition to damaging mature OL, CPZ also reduces NSC/NPC proliferation and activates progenitor migration. These results shed light on CPZ direct effects on NSC proliferation and the progression of in vitro differentiation.
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ispartof Molecular neurobiology, 2023-03, Vol.60 (3), p.1195-1213
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subjects Animal models
Animals
Astrocytes
Biomedical and Life Sciences
Biomedicine
Cell Biology
Cell death
Cell Differentiation
Cell proliferation
Cuprizone
Cuprizone - toxicity
Demyelinating Diseases - metabolism
Demyelination
Gliosis
Lateral Ventricles - metabolism
Mice
Mice, Inbred C57BL
Myelination
Neural stem cells
Neural Stem Cells - metabolism
Neurobiology
Neurology
Neurosciences
Neurospheres
Oligodendrocytes
Oligodendroglia - metabolism
Progenitor cells
Reactive oxygen species
Regeneration
Stem cell transplantation
Stem cells
Subventricular zone
Toxicity
title The Effects of Cuprizone on Murine Subventricular Zone-Derived Neural Stem Cells and Progenitor Cells Grown as Neurospheres
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