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Updated: Jun 17, 2026
An Ex vivo Model of an Oligodendrocyte-directed T-Cell Attack in Acute Brain Slices
Published on: February 5, 2015
Dicer ablation in oligodendrocytes provokes neuronal impairment in mice
Daesung Shin1, Ji-Yeon Shin, Michael T McManus
1Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA.
Objective:
MicroRNAs (miRNAs) regulate gene expression and have many roles in the brain, but a role in oligodendrocyte (OL) function has not been demonstrated.
Methods:
A Dicer floxed conditional allele was crossed with the proteolipid protein promoter-driven inducible Cre allele to generate inducible, OL-specific Dicer-floxed mice.
Results:
OL-specific Dicer mutants show demyelination, oxidative damage, inflammatory astrocytosis and microgliosis in the brain, and eventually neuronal degeneration and shorter lifespan. miR-219 and its target ELOVL7 (elongation of very long chain fatty acids protein 7) were identified as the main molecular components that are involved in the development of the phenotype in these mice. Overexpressing ELOVL7 results in lipid accumulation, which is suppressed by miR-219 co-overexpression. In Dicer mutant brain, excess lipids accumulate in myelin-rich brain regions, and the peroxisomal beta-oxidation activity is dramatically reduced.
Interpretation:
Postnatal Dicer ablation in mature OLs results in inflammatory neuronal degeneration through increased demyelination, lipid accumulation, and peroxisomal and oxidative damage, and therefore indicates that miRNAs play an essential role in the maintenance of lipids and redox homeostasis in mature OLs that are necessary for supporting axonal integrity as well as the formation of compact myelin.
