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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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]
Citations
Cites
Endoplasmic reticulum stress: cell life and death decisions
Xu, C. (2005) · Journal of Clinical Investigation · doi:10.1172/jci26373 · Cited by 2,291
Biology of Oligodendrocyte and Myelin in the Mammalian Central Nervous System
Baumann, N., & Pham-Dinh, D. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.871 · Cited by 1,828
Demyelination increases radial diffusivity in corpus callosum of mouse brain
Song, S.-K., Yoshino, J., Le, T. Q., Lin, S.-J., Sun, S.-W., Cross, A. H., & Armstrong, R. C. (2005) · NeuroImage · doi:10.1016/j.neuroimage.2005.01.028 · Cited by 1,658
Endoplasmic Reticulum Stress and Oxidative Stress: A Vicious Cycle or a Double-Edged Sword?
Malhotra, J. D., & Kaufman, R. J. (2007) · Antioxidants and Redox Signaling · doi:10.1089/ars.2007.1782 · Cited by 1,588
The yin and yang of neurotrophin action
Lu, B., Pang, P. T., & Woo, N. H. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1726 · Cited by 1,356
Bak, L. K., Schousboe, A., & Waagepetersen, H. S. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03913.x · Cited by 1,114
Debris clearance by microglia: an essential link between degeneration and regeneration
Neumann, H., Kotter, M. R., & Franklin, R. J. M. (2008) · Brain · doi:10.1093/brain/awn109 · Cited by 1,111
TNFα promotes proliferation of oligodendrocyte progenitors and remyelination
Arnett, H. A., Mason, J., Marino, M., Suzuki, K., Matsushima, G. K., & Ting, J. P.-Y. (2001) · Nature Neuroscience · doi:10.1038/nn738 · Cited by 1,012
Matsushima, G. K., & Morell, P. (2001) · Brain Pathology · doi:10.1111/j.1750-3639.2001.tb00385.x · Cited by 984
Myelin Impairs CNS Remyelination by Inhibiting Oligodendrocyte Precursor Cell Differentiation
Kotter, M. R., Li, W.-W., Zhao, C., & Franklin, R. J. M. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2615-05.2006 · Cited by 768
Cited by
Sorted by citations
Items 401–435 of 435
Puorro-Radzwill, K., Pang, P. T., Giera, S., Sheng, G., Farley, J. E., Garron, C., Danthi, S. J., Gans, J., Kumar, D., Agrawal, R. G., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.08.659146 · Cited by 2
1 TESLA MRI AND MIP ANALYSIS FOR CUPRIZONE-INDUCED DEMYELINATION ASSESEMENT IN C57BL/6 MICEPreprint
Volodina, V. N., Zaitsev, P., Antonov, S. A., Borets, L., Maksaeva, A. O., Makarov, V., & Zherdeva, V. V. (2025) · Research Square · doi:10.21203/rs.3.rs-7078127/v2
AminKhat, N., Basir, Z., Tabandeh, M. R., Ghotbeddin, Z., & Khazaeel, K. (2025) · Molecular Neurobiology · doi:10.1007/s12035-025-05450-y
Zhang, C., Michael, J. A., Teo, J. D., Song, H., Westerhausen, M. T., Mutuku, S. M., Ellis, S. R., & Don, A. S. (2026) · Angewandte Chemie · doi:10.1002/ange.202524636
Xu, Z., Gao, T., Xie, H. Q., He, Y., Luo, H., Mo, Z., Yang, Y., Peng, W., & Xiao, L. (2025) · Glia · doi:10.1002/glia.70121
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622301
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622304
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622307
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622310
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622298
Wang, N., Wang, M., Jeevaratnam, S., Rosenberg, C. L., Ikezu, T. C., Shue, F., Doss, S. V., Alnobani, A., Martens, Y. A., Wren, M. C., et al. (2022) · Figshare · doi:10.6084/m9.figshare.21622295
Engineering an in vitro model of demyelinated spinal cord tissuePreprint
Jin, L., Brinkley, N. T., Tai, Y., Flores, G., & Nam, J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.15.706037
Zhang, C., Michael, J. A., Teo, J. D., Song, H., Westerhausen, M. T., Mutuku, S. M., Ellis, S. R., & Don, A. S. (2026) · Angewandte Chemie International Edition · doi:10.1002/anie.202524636
Adkins-Travis, K., Song, M.-G., Schwaiger-Haber, M., Cho, K., Fowle-Grider, R., Johnson, S. L., Shriver, L. P., & Patti, G. J. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.03.19.712965
Byrne, A. J., Pibuel, M. A., Martínez, J. M. L., & Franco, P. G. (2026) · Journal of Neurochemistry · doi:10.1111/jnc.70422
Myelin imaging in MRI using ultra-short echo time sequences
Soustelle, L. (2018) · theses.fr (ABES) · doi:10.70675/7606cd78z6ce3z466fzbba0z59ebf521f1d9
Le cil primaire : une nouvelle cible pour la remyélinisation ?
Delfino, G. (2020) · theses.fr (ABES) · doi:10.70675/a62c179az64bfz4247zb041zc7cfc961677c
Panichnantakul, P., Shaw, R., Burianova, V. K., McErlain, H., Sutherland, A., Williams, A., Waldman, A. D., & Tavares, A. A. S. (2026) · EJNMMI Research · doi:10.1186/s13550-026-01391-2
Bai, G., Zhou, X., Xiong, C., Kang, X., Huang, R., Bai, D., Zhao, P., Tao, P., Muer, C., Jiang, G., et al. (2026) · PLoS ONE · doi:10.1371/journal.pone.0347526
Bernaerts, E., Rutten, M., Visscher, A. D., Beliën, J., Berghmans, N., Mitera, T., Somer, L. D., Matthys, P., & Vandooren, J. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05905-w · Cited by 1
Gaydarski, L., Petrova, K., Stamenov, N., Iliev, A. A., Stanchev, S., Rashev, P., Pupaki, D. V., Mourdjeva, M., Kostadinova, I., & Landzhov, B. V. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27104519
Nourmohammadi, F., Javan, A., Shirzad, M., Sadeghi, F., & Ghasemi‐Kasman, M. (2026) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2026.111967
Vu, H., George, N., & Xiao, J. (2026) · Cellular and molecular neurobiology · doi:10.1007/s10571-026-01748-0
Polyák, H., Galla, Z., Martos, D., Rajda, C., Monostori, P. B., Klivènyi, P., & Vécsei, L. (2026) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2026.111795
Moussaoui, H., Amarni, M., Ladjel‐Mendil, A., Saada, M.-C., Moslah, W., Merzouagui, R., Srairi‐Abid, N., & Laraba‐Djebari, F. (2026) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-026-10842-2
Herdt, D. D., Lefevere, E., Brouwers, V., Hartvig, L., Geeraerts, E., Hsiao, C., Chen, J. Q. A., Pinto, R., Duvey, G., Burbidge, S., et al. (2026) · PLoS ONE · doi:10.1371/journal.pone.0354525
Tsai, H., Piya, S., Wang, J., Zhu, J., Hu, W., Gehrke, A. R., Cao, S., Guise, A. J., Chan, S. J., Sheehan, M. J., et al. (2026) · Frontiers in Bioinformatics · doi:10.3389/fbinf.2026.1832826 · Cited by 2
Walters, E. H., Censo, D. D., Samoylenko, E., Kim, E., Loomis, S., Papaonisiforou, C., Simmons, C., Flower, G., Ilić, K., MacNicol, E., et al. (2026) · Experimental Neurology · doi:10.1016/j.expneurol.2026.115963
Oligodendrocyte and Astrocyte Dynamics During Short‐Term Cuprizone Treatment
Frankle, L., Oso, M. O., Riley, A., Tomor, R., Checan, D. C., Lee, H., Jarzembak, K., Sternbach, S., Shelestak, J., McDonough, J. A., et al. (2026) · Brain and Behavior · doi:10.1002/brb3.71660
Noori, T., Hosseini, S. Z., Korani, S., Alavi, S. D., Heidarizade, N., Mohammadi-Farani, A., & Shirooie, S. (2026) · Journal of Medicinal Plants · doi:10.66224/jmp.25.98.1
Behairy, S., Fahmy, M. I., Sayed, R. H., & El-Yamany, M. F. (2026) · Journal of Pharmacy and Pharmacology · doi:10.1093/jpp/rgag113
Shimshek, D. R., Zurbruegg, S., Neuhaus, A., Doelemeyer, A., & Beckmann, N. (2026) · Aging Brain · doi:10.1016/j.nbas.2026.100171
Judai, R. R., Shiha, N. A., Fattah, M. A. E. E. D. A. E., & Sayed, N. S. E. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.117614
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
