Distribution of oligodendrocyte loss and mitochondrial toxicity in the cuprizone-induced experimental demyelination model

Cuprizone selectively affects oligodendrocytes.

“Nevertheless, a consensus seems to be that cuprizone selectively affects oligodendrocytes.”

Cuprizone administration induces mitochondrial enlargement, alters metabolic rates, and impairs oxidative phosphorylation by reducing copper-containing mitochondrial enzymes such as monoamine oxidase and cytochrome c oxidase in the brain of mice.

“Cuprizone administration induces mitochondrial enlargement, severely alters metabolic rates, and impairs oxidative phosphorylation by reducing mitochondrial enzymes that contain copper as a cofactor, such as monoamine oxidase [27] and cytochrome c (Cyt c) oxidase [28, 29] in the brain of mice.”

Cuprizone ingestion alters mitochondria in the CNS of mice.

“Cuprizone ingestion alters mitochondria in the CNS of mice [27–29, 109].”

Cuprizone administration reduces the mitochondrial enzymes monoamine oxidase (as early as 3 days) and cytochrome c oxidase in the brain of mice, both of which require copper for catalysis.

“For example, cuprizone administration reduces the mitochondrial enzymes monoamine oxidase (as early as 3 days [27]) and cyt c oxidase [28, 29] in the brain of mice, both of which require copper for catalysis [126].”

Early after cuprizone administration, ROS production increases coincident with mitochondrial and metabolic dysfunction that could directly cause oligodendrocyte death.

“Early after cuprizone administration, ROS production increases coincident with mitochondrial and metabolic dysfunction that could directly cause oligodendrocyte death [28, 29, 101, 243].”