The DOI matches its Crossref record; 268 of the 268 references it cites were found in a registry or an index.
Cellular and molecular neuropathology of the cuprizone mouse model: Clinical relevance for multiple sclerosis
Open accessAbstract
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.
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In the citing paper
“Importantly this apoptosis precedes the massive demyelination caused by cuprizone administration [18], indicating that oligodendrocyte degeneration is the main cause, as opposed to a secondary immune response.”
From Strain differences in cuprizone induced demyelination (2017) · cites this paper as [18]
In the citing paper
“In addition to the direct effect of cuprizone on oligodendrocytes, the involvement of the brain’s resident neuroinflammatory cells such as microglia and astrocyes is also believed to be responsible for the massive demyelination occurring at 4 weeks time point of cuprizone exposure [18].”
From Strain differences in cuprizone induced demyelination (2017) · cites this paper as [18]
In the citing paper
“Nevertheless, a consensus seems to be that cuprizone selectively affects oligodendrocytes.”
From Strain differences in cuprizone induced demyelination (2017) · cites this paper as [18]
In the citing paper
“Astrocytes and microglia collaborate through the release of cytokines, chemokines, and other, yet to be identified factors, to drive demyelination [79, 107], preventing the release of specific cytokines or chemokines, restricting astrocyte reactivity, or ablating microglia all reduce cuprizone-induced demyelination [107, 181, 189, 243].”
From Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination (2022) · cites this paper as [107]
In the citing paper
“The cuprizone model is based on oral ingestion of the copper chelator cuprizone, causing metabolic oligodendrocyte injury.”
From Insights and challenges on animal models for progressive multiple sclerosis (2026) · cites this paper as [183]
In the citing paper
“These include cuprizone (CUP), a chemical toxin, which when provided in the diet of adult mice results in reliable demyelination of the corpus callosum (CC). Upon removal of CUP from the diet, there is robust remyelination (Matsushima & Morrell, 2001; Praet, et al, 2014; Wergeland, Torkildsen, Myhr, Mørk, & Bø et al, 2012).”
From Activated microglia drive demyelination via CSF1R signaling (2021) · cites this paper as Praet, et al, 2014
In the citing paper
“In the following chapter we will briefly introduce the cuprizone model, a toxin-induced demyelination model [21,22].”
From The Cuprizone Model: Dos and Do Nots (2020) · cites this paper as [22]
In the citing paper
“Oral intoxication with the copper-chelator cuprizone induces oligodendrocyte apoptosis within a few days, which is closely followed by the activation of the innate immune cells in the brain, i.e., astrocytes and microglia, finally leading to demyelination of distinct white and grey matter brain areas.”
From The Cuprizone Model: Dos and Do Nots (2020) · cites this paper as [22]
In the citing paper
“Mitochondrial injury and oxidative stress are believed to be fundamental elements of CPZ induced pathology (66).”
From Absence of miRNA-146a Differentially Alters Microglia Function and Proteome (2020) · cites this paper as [66]
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Metadata
- Authors
- Praet, J., Guglielmetti, C., Berneman, Z., Van der Linden, A., & Ponsaerts, P.
- Affiliations
- University of Antwerp (BE)
- Corresponding author
- Praet, Jelle
- Venue
- Neuroscience & Biobehavioral Reviews
- Publisher
- Elsevier BV
- Published
- 2014-11
- Volume
- 47
- Pages
- 485-505
- ISSN
- 0149-7634 (ISSN-L)
- OpenAlex
- W1991883207
- Cited by
- 435
- References
- 268
- Citations by year
- 2026: 29 · 2025: 36 · 2024: 29 · 2023: 37 · 2022: 51 · 2021: 49 · 2020: 48 · 2019: 49 · 2018: 41 · 2017: 35 · 2016: 19 · 2015: 12
- FWCI
- 3.11
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuroscience & Biobehavioral Reviews (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Fund for Scientific Research-Flanders
- Topics
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- cuprizone, multiple sclerosis, demyelination, remyelination, oligodendrocyte apoptosis, myelin degeneration, metabolic stress, neuroinflammation, neurotrophic factors, myelin debris clearance, axonal pathology, neuronal pathology, schizophrenia, epilepsy, mouse model
- MeSH terms
- Animals, Brain, Cuprizone, Disease Models, Animal, Multiple Sclerosis, Myelin Sheath, Neuroglia, Neurons, Oxidative Stress, Mice
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