Mitochondrial complex IV is lost in neurons in the cuprizone mouse model.

Mitochondrial complex IV is lost in neurons in the cuprizone mouse model.

Publication date: Oct 31, 2019

Cuprizone administration in mice leads to oligodendrocyte death and demyelination. The effect is thought to reflect copper-chelation that leads to inhibition of complex IV of the mitochondrial respiratory chain. The effects this drug has on neurons are less well known.

To investigate the toxic effects of cuprizone on mitochondria in neurons.

Male c57Bl/6 mice were fed 0.2% cuprizone for up to 5 weeks. Cuprizone-fed and control mice were examined at week 1, 3, 5 and 4 weeks after cessation of cuprizone exposure. The brain was examined for myelin, complex I, complex IV and for COX/SDH activities. Mitochondrial-DNA was investigated for deletions and copy number variation.

We found decreased levels of complex IV in the cerebellar Purkinje neurons of mice exposed to cuprizone. This decrease was not related to a general decrease in mitochondrial volume or mass, as there were no differences in the levels of complex I or TOMM20.

Neurons are affected by cuprizone-treatment. Whether this mitochondrial dysfunction acts as a subclinical trigger for demyelination and the long-term axonal degeneration that proceeds after cuprizone treatment stops remains unclear.

Varhaug, K.N., Krakenes, T., Alme, M.N., Vedeler, C.A., and Bindoff, L.A. Mitochondrial complex IV is lost in neurons in the cuprizone mouse model. 19403. 2019 Mitochondrion.

Concepts Keywords
Brain Oligodendrocyte death demyelination
Cerebellar Branches of biology
Chelation Senescence
Copper Mitochondrial genetics
Demyelination Medical terminology
DNA Neuron
Mitochondria Mitochondrion
Mitochondrial Mitochondrial DNA
Mitochondrial Respiratory Chain TOMM20
Mitochondrion Neurodegeneration
Myelin Myelin
Neurons Transneuronal degeneration
Oligodendrocyte SDH
Purkinje Neurons
SDH

Semantics

Type Source Name
disease MESH death
disease MESH demyelination
drug DRUGBANK Copper
gene UNIPROT CPOX
gene UNIPROT SORD
gene UNIPROT SDHB
gene UNIPROT SDS
gene UNIPROT TOMM20
disease MESH multiple sclerosis
disease DOID multiple sclerosis

Original Article

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