Five Decades of Cuprizone, an Updated Model to Replicate Demyelinating Diseases

INTRODUCTION: Demyelinating diseases of the central nervous system (CNS) comprise a group of neurological dis-orders characterized by progressive (and eventually irreversible) loss of oligodendrocytes and myelin sheaths in the white matter tracts. Some of myelin disorders include: Multiple sclerosis, Guillain-Barré syndrome, peripheral nerve polyneuropa-thy and others. To date, the etiology of these disorders is not well known and no effective treatments are currently available against them. Therefore, further research is needed to gain a better understand and treat these patients. To accomplish this goal, it is necessary to have appropriate animal models that closely resemble the pathophysiolo-gy and clinical signs of these diseases. Herein, we describe the model of toxic demyelination induced by cuprizone (CPZ), a copper chelator that reduces the cytochrome and monoamine oxidase activity into the brain, produces mitochondrial stress and triggers the local immune response. These biochemical and cellular responses ultimately result in selective loss of oli-godendrocytes and microglia accumulation, which conveys to extensive areas of demyelination and gliosis in corpus callo-sum, superior cerebellar peduncles and cerebral cortex. Remarkably, some aspects of the histological pattern induced by CPZ are similar to those found in multiple sclerosis. CPZ exposure provokes behavioral changes, impairs motor skills and affects mood as that observed in several de-myelinating diseases. Upon CPZ removal, the pathological and histological changes gradually revert. Therefore, some au-thors have postulated that the CPZ model allows to partially mimic the disease relapses observed in some demyelinating dis-eases. CONCLUSION: for five decades, the model of CPZ-induced demyelination is a good experimental approach to study demye-linating diseases that has maintained its validity, and is a suitable pharmacological model for reproducing some key features of demyelinating diseases, including multiple sclerosis.