TY - JOUR
T1 - Cellular and molecular neuropathology of the cuprizone mouse model
T2 - Clinical relevance for multiple sclerosis
AU - Praet, Jelle
AU - Guglielmetti, Caroline
AU - Berneman, Zwi
AU - Van der Linden, Annemie
AU - Ponsaerts, Peter
N1 - Publisher Copyright:
© 2014 The Authors.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - The cuprizone mouse model allows the investigation of the complex molecular mechanisms behind nonautoimmune-mediated demyelination and spontaneous remyelination. While it is generally accepted that oligodendrocytes are specifically vulnerable to cuprizone intoxication due to their high metabolic demands, a comprehensive overview of the etiology of cuprizone-induced pathology is still missing to date. In this review we extensively describe the physico-chemical mode of action of cuprizone and discuss the molecular and enzymatic mechanisms by which cuprizone induces metabolic stress, oligodendrocyte apoptosis, myelin degeneration and eventually axonal and neuronal pathology. In addition, we describe the dual effector function of the immune system which tightly controls demyelination by effective induction of oligodendrocyte apoptosis, but in contrast also paves the way for fast and efficient remyelination by the secretion of neurotrophic factors and the clearance of cellular and myelinic debris. Finally, we discuss the many clinical symptoms that can be observed following cuprizone treatment, and how these strengthened the cuprizone model as a useful tool to study human multiple sclerosis, schizophrenia and epilepsy.
AB - The cuprizone mouse model allows the investigation of the complex molecular mechanisms behind nonautoimmune-mediated demyelination and spontaneous remyelination. While it is generally accepted that oligodendrocytes are specifically vulnerable to cuprizone intoxication due to their high metabolic demands, a comprehensive overview of the etiology of cuprizone-induced pathology is still missing to date. In this review we extensively describe the physico-chemical mode of action of cuprizone and discuss the molecular and enzymatic mechanisms by which cuprizone induces metabolic stress, oligodendrocyte apoptosis, myelin degeneration and eventually axonal and neuronal pathology. In addition, we describe the dual effector function of the immune system which tightly controls demyelination by effective induction of oligodendrocyte apoptosis, but in contrast also paves the way for fast and efficient remyelination by the secretion of neurotrophic factors and the clearance of cellular and myelinic debris. Finally, we discuss the many clinical symptoms that can be observed following cuprizone treatment, and how these strengthened the cuprizone model as a useful tool to study human multiple sclerosis, schizophrenia and epilepsy.
KW - Cuprizone
KW - Demyelination
KW - Epilepsy
KW - Metabolic stress
KW - Multiple sclerosis
KW - Myelin
KW - Neuroinflammation
KW - Oligodendrocyte
KW - Remyelination
KW - Schizophrenia
UR - http://www.scopus.com/inward/record.url?scp=84908670613&partnerID=8YFLogxK
U2 - 10.1016/j.neubiorev.2014.10.004
DO - 10.1016/j.neubiorev.2014.10.004
M3 - Review article
C2 - 25445182
AN - SCOPUS:84908670613
SN - 0149-7634
VL - 47
SP - 485
EP - 505
JO - Neuroscience and Biobehavioral Reviews
JF - Neuroscience and Biobehavioral Reviews
ER -