cuprizone

Summary

Summary: Copper chelator that inhibits monoamine oxidase and causes liver and brain damage.

Top Publications

  1. Matsushima G, Morell P. The neurotoxicant, cuprizone, as a model to study demyelination and remyelination in the central nervous system. Brain Pathol. 2001;11:107-16 pubmed
    ..demyelination can be reproducibly induced in large areas of mouse brain is exposure to the copper chelator, cuprizone, in the diet...
  2. Patel J, McCandless E, Dorsey D, Klein R. CXCR4 promotes differentiation of oligodendrocyte progenitors and remyelination. Proc Natl Acad Sci U S A. 2010;107:11062-7 pubmed publisher
    ..Using an experimental murine model of demyelination mediated by the copper chelator cuprizone, we evaluated the expression of CXCL12 and its receptor, CXCR4, within the demyelinating and remyelinating ..
  3. Cate H, Sabo J, Merlo D, Kemper D, Aumann T, Robinson J, et al. Modulation of bone morphogenic protein signalling alters numbers of astrocytes and oligodendroglia in the subventricular zone during cuprizone-induced demyelination. J Neurochem. 2010;115:11-22 pubmed publisher
    ..context we undertook a microarray and quantitative PCR based analysis of genes expressed within the SVZ during cuprizone-induced demyelination...
  4. Mason J, Langaman C, Morell P, Suzuki K, Matsushima G. Episodic demyelination and subsequent remyelination within the murine central nervous system: changes in axonal calibre. Neuropathol Appl Neurobiol. 2001;27:50-8 pubmed
    Exposure of young adult C57BL/6 mice to cuprizone in the diet initiated profound and synchronous demyelination of the corpus callosum, which was virtually complete by 4 weeks of exposure...
  5. Skripuletz T, Miller E, Moharregh Khiabani D, Blank A, Pul R, Gudi V, et al. Beneficial effects of minocycline on cuprizone induced cortical demyelination. Neurochem Res. 2010;35:1422-33 pubmed publisher
    In this study, we investigated the potential of minocycline to influence cuprizone induced demyelination in the grey and white matter...
  6. Hesse A, Wagner M, Held J, Bruck W, Salinas Riester G, Hao Z, et al. In toxic demyelination oligodendroglial cell death occurs early and is FAS independent. Neurobiol Dis. 2010;37:362-9 pubmed publisher
    ..The underlying mechanisms are largely unknown. Here, we demonstrate that in the toxic demyelination cuprizone model, oligodendroglial cell death and downregulation of myelin genes start days after initiation of the ..
  7. Hiremath M, Saito Y, Knapp G, Ting J, Suzuki K, Matsushima G. Microglial/macrophage accumulation during cuprizone-induced demyelination in C57BL/6 mice. J Neuroimmunol. 1998;92:38-49 pubmed
    To study microglial/macrophage infiltration, a cuprizone-induced model for demyelination in C57BL/6 mice was established...
  8. Hoehn H, Kress Y, Sohn A, Brosnan C, Bourdon S, Shafit Zagardo B. Axl-/- mice have delayed recovery and prolonged axonal damage following cuprizone toxicity. Brain Res. 2008;1240:1-11 pubmed publisher
    ..To evaluate Axl's role in brain during cuprizone toxicity, mice were fed cuprizone and evaluated at 3-, 4-, and 6-week cuprizone treatment and 3- and 5-week post-..
  9. Zhang Y, Zhang H, Wang L, Jiang W, Xu H, Xiao L, et al. Quetiapine enhances oligodendrocyte regeneration and myelin repair after cuprizone-induced demyelination. Schizophr Res. 2012;138:8-17 pubmed publisher
    ..C57BL/6 mice were fed with cuprizone (0...

More Information

Publications62

  1. Skripuletz T, Gudi V, Hackstette D, Stangel M. De- and remyelination in the CNS white and grey matter induced by cuprizone: the old, the new, and the unexpected. Histol Histopathol. 2011;26:1585-97 pubmed publisher
    The copper chelator cuprizone (bis-cyclohexanone oxaldihydrazone) was established as a neurotoxin in rodents in 1966 by Carlton...
  2. Gao X, Gillig T, Ye P, D Ercole A, Matsushima G, Popko B. Interferon-gamma protects against cuprizone-induced demyelination. Mol Cell Neurosci. 2000;16:338-49 pubmed
    ..Mice that receive through their diet the copper chelator cuprizone display extensive demyelination of the corpus callosum...
  3. Liu L, Belkadi A, Darnall L, Hu T, Drescher C, Cotleur A, et al. CXCR2-positive neutrophils are essential for cuprizone-induced demyelination: relevance to multiple sclerosis. Nat Neurosci. 2010;13:319-26 pubmed publisher
    ..For mice of susceptible strains, cuprizone feeding results in oligodendrocyte cell loss and demyelination of the corpus callosum...
  4. Zhang Y, Xu H, Jiang W, Xiao L, Yan B, He J, et al. Quetiapine alleviates the cuprizone-induced white matter pathology in the brain of C57BL/6 mouse. Schizophr Res. 2008;106:182-91 pubmed publisher
    ..In the present study, C57BL/6 mice were given 0.2% cuprizone (CPZ) in their diet for five weeks during which they drank distilled water without or with quetiapine (QTP, 10 ..
  5. Crocker S, Bajpai R, Moore C, Frausto R, Brown G, Pagarigan R, et al. Intravenous administration of human embryonic stem cell-derived neural precursor cells attenuates cuprizone-induced central nervous system (CNS) demyelination. Neuropathol Appl Neurobiol. 2011;37:643-53 pubmed publisher
    ..v.) administration of hES-NPCs would impact central nervous system (CNS) demyelination in a cuprizone model of demyelination. C57Bl/6 mice were fed cuprizone (0...
  6. Palumbo S, Toscano C, Parente L, Weigert R, Bosetti F. The cyclooxygenase-2 pathway via the PGEâ‚‚ EP2 receptor contributes to oligodendrocytes apoptosis in cuprizone-induced demyelination. J Neurochem. 2012;121:418-27 pubmed publisher
    ..However, it is not known whether COX-2 activity contributes to oligodendrocyte death. In cuprizone-induced demyelination, oligodendrocyte apoptosis and a concomitant increase in the gene expression of COX-2 and ..
  7. Pasquini L, Calatayud C, Bertone Uña A, Millet V, Pasquini J, Soto E. The neurotoxic effect of cuprizone on oligodendrocytes depends on the presence of pro-inflammatory cytokines secreted by microglia. Neurochem Res. 2007;32:279-92 pubmed
    In order to further characterize the still unknown mechanism of cuprizone-induced demyelination, we investigated its effect on rat primary oligodendroglial cell cultures. Cell viability was not significantly affected by this treatment...
  8. Song S, Yoshino J, Le T, Lin S, Sun S, Cross A, et al. Demyelination increases radial diffusivity in corpus callosum of mouse brain. Neuroimage. 2005;26:132-40 pubmed
    ..The current study uses the well-characterized cuprizone model of experimental demyelination and remyelination of corpus callosum in mouse brain to evaluate the ability ..
  9. Zendedel A, Beyer C, Kipp M. Cuprizone-induced demyelination as a tool to study remyelination and axonal protection. J Mol Neurosci. 2013;51:567-72 pubmed publisher
    ..The focus of the discussion is the relevance of the toxin model 'cuprizone' to study the pathology of demyelination and the physiology of remyelination...
  10. Hibbits N, Yoshino J, Le T, Armstrong R. Astrogliosis during acute and chronic cuprizone demyelination and implications for remyelination. ASN Neuro. 2012;4:393-408 pubmed publisher
    ..current study characterizes these glial populations relative to expression of candidate regulatory molecules in cuprizone demyelinated corpus callosum...
  11. Gudi V, Skuljec J, Yildiz O, Frichert K, Skripuletz T, Moharregh Khiabani D, et al. Spatial and temporal profiles of growth factor expression during CNS demyelination reveal the dynamics of repair priming. PLoS ONE. 2011;6:e22623 pubmed publisher
    ..We employed the well established murine cuprizone model of toxic demyelination to analyze the expression of 13 growth factors in the CNS during de- and ..
  12. Kipp M, Gingele S, Pott F, Clarner T, van der Valk P, Denecke B, et al. BLBP-expression in astrocytes during experimental demyelination and in human multiple sclerosis lesions. Brain Behav Immun. 2011;25:1554-68 pubmed publisher
    ..Using the well-established toxic demyelination cuprizone model, we created lesions with either robust or impaired endogenous remyelination capacity...
  13. Pott F, Gingele S, Clarner T, Dang J, Baumgartner W, Beyer C, et al. Cuprizone effect on myelination, astrogliosis and microglia attraction in the mouse basal ganglia. Brain Res. 2009;1305:137-49 pubmed publisher
    ..appropriate animal model for studying cortical deep grey matter demyelination is established, we reassessed the cuprizone mouse model to investigate basal ganglia demyelination. Mice were fed cuprizone for different time intervals...
  14. Mason J, Xuan S, Dragatsis I, Efstratiadis A, Goldman J. Insulin-like growth factor (IGF) signaling through type 1 IGF receptor plays an important role in remyelination. J Neurosci. 2003;23:7710-8 pubmed
    ..in the mouse brain by Cre-mediated recombination and then exposing these mutants and normal siblings to cuprizone. This neurotoxicant induces a demyelinating lesion in the corpus callosum that is reversible on termination of ..
  15. Acs P, Komoly S. Selective ultrastructural vulnerability in the cuprizone-induced experimental demyelination. Ideggyogy Sz. 2012;65:266-70 pubmed
    ..The copper chelator cuprizone induces primary oligodendrocyte apoptosis and consequent demyelination in well defined areas of the mouse brain...
  16. Xu H, Yang H, Zhang Y, Clough R, Browning R, Li X. Behavioral and neurobiological changes in C57BL/6 mice exposed to cuprizone. Behav Neurosci. 2009;123:418-29 pubmed publisher
    C57BL/6 mice were given 0.2% cuprizone (CPZ) for 2 to 6 weeks while controls ate the same diet without CPZ. At various time points the animals were subjected to behavioral tests and their brains were analyzed...
  17. Millet V, Moiola C, Pasquini J, Soto E, Pasquini L. Partial inhibition of proteasome activity enhances remyelination after cuprizone-induced demyelination. Exp Neurol. 2009;217:282-96 pubmed publisher
    ..On the other hand, we have recently shown that the mechanism of cuprizone toxicity on oligodendroglial cells involves the recruitment of microglia and their secretion of pro-inflammatory ..
  18. Groebe A, Clarner T, Baumgartner W, Dang J, Beyer C, Kipp M. Cuprizone treatment induces distinct demyelination, astrocytosis, and microglia cell invasion or proliferation in the mouse cerebellum. Cerebellum. 2009;8:163-74 pubmed publisher
    ..In this study, we used the cuprizone mouse model to investigate cerebellar demyelination in young adult male mice...
  19. Herring N, Konradi C. Myelin, copper, and the cuprizone model of schizophrenia. Front Biosci (Schol Ed). 2011;3:23-40 pubmed
    ..one particular experimental model for the study of dysmyelination, created by the administration of the toxin cuprizone. Cuprizone, a copper chelator, causes white matter abnormalities in rodents...
  20. Jurevics H, Hostettler J, Muse E, Sammond D, Matsushima G, Toews A, et al. Cerebroside synthesis as a measure of the rate of remyelination following cuprizone-induced demyelination in brain. J Neurochem. 2001;77:1067-76 pubmed
    ..We also studied mice exposed to a diet containing 0.2% of the copper chelator, cuprizone. After 6 weeks 20%, and by 12 weeks, over 30% of brain cerebroside was gone...
  21. Benardais K, Kotsiari A, Skuljec J, Koutsoudaki P, Gudi V, Singh V, et al. Cuprizone [bis(cyclohexylidenehydrazide)] is selectively toxic for mature oligodendrocytes. Neurotox Res. 2013;24:244-50 pubmed publisher
    b>Cuprizone [bis(cyclohexylidenehydrazide)]-induced toxic demyelination is an experimental animal model commonly used to study de- and remyelination in the central nervous system...
  22. Vondran M, Singh H, Honeywell J, Dreyfus C. Levels of BDNF impact oligodendrocyte lineage cells following a cuprizone lesion. J Neurosci. 2011;31:14182-90 pubmed publisher
    ..In this study, to investigate the roles BDNF may play in the repair of a demyelinating lesion, the cuprizone model was used and the corpus callosum was examined...
  23. Franco Pons N, Torrente M, Colomina M, Vilella E. Behavioral deficits in the cuprizone-induced murine model of demyelination/remyelination. Toxicol Lett. 2007;169:205-13 pubmed
    The neurotoxicant cuprizone has been used extensively to create a mouse model of demyelination. However, the effects on behavior of cuprizone treatment have not been previously reported...
  24. Biancotti J, Kumar S, de Vellis J. Activation of inflammatory response by a combination of growth factors in cuprizone-induced demyelinated brain leads to myelin repair. Neurochem Res. 2008;33:2615-28 pubmed publisher
    In vivo remyelination promoted by a combination of four oligodendrocyte specific growth factors (GFs) in cuprizone-induced demyelinated mice brains was described recently by our group...
  25. Steelman A, Thompson J, Li J. Demyelination and remyelination in anatomically distinct regions of the corpus callosum following cuprizone intoxication. Neurosci Res. 2012;72:32-42 pubmed publisher
    ..However, this process ceases in later stages despite the presence of pre-oligodendrocytes. Cuprizone-induced demyelination is a useful model with which to study the remyelination process...
  26. McMahon E, Cook D, Suzuki K, Matsushima G. Absence of macrophage-inflammatory protein-1alpha delays central nervous system demyelination in the presence of an intact blood-brain barrier. J Immunol. 2001;167:2964-71 pubmed
    ..Here, we describe the role of macrophage inflammatory protein-1alpha (MIP-1alpha) during cuprizone intoxication, a model where demyelination of the CNS features a large accumulation of microglia/macrophage ..
  27. Vana A, Flint N, Harwood N, Le T, Fruttiger M, Armstrong R. Platelet-derived growth factor promotes repair of chronically demyelinated white matter. J Neuropathol Exp Neurol. 2007;66:975-88 pubmed
    ..growth factor-A (PDGF-A) in recovery from chronic demyelination we induced corpus callosum demyelination using cuprizone treatment in hPDGF-A transgenic (tg) mice with the human PDGF-A gene under control of an astrocyte-specific ..
  28. Moody L, Herbst A, Yoo H, Vanderloo J, Aiken J. Comparative prion disease gene expression profiling using the prion disease mimetic, cuprizone. Prion. 2009;3:99-109 pubmed
    ..b>Cuprizone, a neurotoxicant, qualitatively mimics the cell population changes observed in prion disease, resulting in both ..
  29. Tsiperson V, Li X, Schwartz G, Raine C, Shafit Zagardo B. GAS6 enhances repair following cuprizone-induced demyelination. PLoS ONE. 2010;5:e15748 pubmed publisher
    ..that administration of recombinant human Gas6 (rhGas6) protein into the CNS improves recovery following cuprizone withdrawal...
  30. Clarner T, Parabucki A, Beyer C, Kipp M. Corticosteroids impair remyelination in the corpus callosum of cuprizone-treated mice. J Neuroendocrinol. 2011;23:601-11 pubmed publisher
    ..the expression of cellular and molecular markers of spontaneous endogenous remyelination in the toxic non-immune cuprizone animal model at early (9 days) and intermediate (21 days) remyelination, as well as steroidal effects in primary ..
  31. Koutsoudaki P, Skripuletz T, Gudi V, Moharregh Khiabani D, Hildebrandt H, Trebst C, et al. Demyelination of the hippocampus is prominent in the cuprizone model. Neurosci Lett. 2009;451:83-8 pubmed publisher
    ..We have previously reported that in the murine cuprizone model for demyelination lesions occur in addition to the corpus callosum also in the neocortex and hippocampus...
  32. Mason J, Toews A, Hostettler J, Morell P, Suzuki K, Goldman J, et al. Oligodendrocytes and progenitors become progressively depleted within chronically demyelinated lesions. Am J Pathol. 2004;164:1673-82 pubmed
    ..mechanisms that may underlie the progression of a demyelinated lesion to a chronic state, we have used the cuprizone model of chronic demyelination...
  33. Baertling F, Kokozidou M, Pufe T, Clarner T, Windoffer R, Wruck C, et al. ADAM12 is expressed by astrocytes during experimental demyelination. Brain Res. 2010;1326:1-14 pubmed publisher
    ..As pathological paradigm, we used the cuprizone demyelination model in which myelin loss during multiple sclerosis is imitated...
  34. Thiessen J, Zhang Y, Zhang H, Wang L, Buist R, Del Bigio M, et al. Quantitative MRI and ultrastructural examination of the cuprizone mouse model of demyelination. NMR Biomed. 2013;26:1562-81 pubmed publisher
    The cuprizone mouse model of demyelination was used to investigate the influence that white matter changes have on different magnetic resonance imaging results...
  35. Bedard A, Tremblay P, Chernomoretz A, Vallières L. Identification of genes preferentially expressed by microglia and upregulated during cuprizone-induced inflammation. Glia. 2007;55:777-89 pubmed
    ..all of these genes were upregulated in activated microglia after treatment with the demyelinating toxin cuprizone, suggesting that they play roles in neuroinflammation...
  36. Zhang J, Jones M, McMahon M, Mori S, Calabresi P. In vivo and ex vivo diffusion tensor imaging of cuprizone-induced demyelination in the mouse corpus callosum. Magn Reson Med. 2012;67:750-9 pubmed publisher
    ..the differences between in vivo and ex vivo fractional anisotropy and diffusivity measurements in the mouse cuprizone model...
  37. Kumar S, Biancotti J, Yamaguchi M, de Vellis J. Combination of growth factors enhances remyelination in a cuprizone-induced demyelination mouse model. Neurochem Res. 2007;32:783-97 pubmed
    ..PDGF-AA, bFGF, NT3 and IGF-1 are known to regulate OL proliferation, survival and/or differentiation. Following cuprizone-induced demyelination in mice a combination of above four growth factors (GF) was intracranially injected to ..
  38. Kipp M, Clarner T, Gingele S, Pott F, Amor S, van der Valk P, et al. Brain lipid binding protein (FABP7) as modulator of astrocyte function. Physiol Res. 2011;60 Suppl 1:S49-60 pubmed
    ..The relevance of our findings and data from other groups are highlighted and discussed in this paper in the context of myelin repair. ..
  39. Zhou Y, Pannu R, Le T, Armstrong R. Fibroblast growth factor 1 (FGFR1) modulation regulates repair capacity of oligodendrocyte progenitor cells following chronic demyelination. Neurobiol Dis. 2012;45:196-205 pubmed publisher
    ..FGFR1 was found to be upregulated in the corpus callosum during cuprizone mediated demyelination and expressed on OP cells just prior to remyelination...
  40. Buschmann J, Berger K, Awad H, Clarner T, Beyer C, Kipp M. Inflammatory response and chemokine expression in the white matter corpus callosum and gray matter cortex region during cuprizone-induced demyelination. J Mol Neurosci. 2012;48:66-76 pubmed publisher
    ..current study, we compared the kinetics and extent of microglia and astrocyte activation during early and late cuprizone-induced demyelination in the white matter tract corpus callosum and the telencephalic gray matter...
  41. Shen S, Sandoval J, Swiss V, Li J, Dupree J, Franklin R, et al. Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency. Nat Neurosci. 2008;11:1024-34 pubmed publisher
    ..can be recapitulated in vivo in mice receiving systemic administration of pharmacological HDAC inhibitors during cuprizone treatment and is consistent with in vitro results showing defective differentiation of oligodendrocyte ..
  42. Mason J, Suzuki K, Chaplin D, Matsushima G. Interleukin-1beta promotes repair of the CNS. J Neurosci. 2001;21:7046-52 pubmed
    ..Thus, IL-1beta may be crucial to the repair of the CNS, presumably through the induction of astrocyte and microglia-macrophage-derived IGF-1. ..
  43. Jurevics H, Largent C, Hostettler J, Sammond D, Matsushima G, Kleindienst A, et al. Alterations in metabolism and gene expression in brain regions during cuprizone-induced demyelination and remyelination. J Neurochem. 2002;82:126-36 pubmed
    Exposure of mice to the copper chelator, cuprizone, results in CNS demyelination. There is remyelination after removal of the metabolic insult...
  44. Armstrong R, Le T, Frost E, Borke R, Vana A. Absence of fibroblast growth factor 2 promotes oligodendroglial repopulation of demyelinated white matter. J Neurosci. 2002;22:8574-85 pubmed
    ..The cuprizone neurotoxicant model causes extensive corpus callosum demyelination without a lymphocytic cell response...
  45. Wergeland S, Torkildsen Ø, Myhr K, Aksnes L, Mørk S, Bø L. Dietary vitamin D3 supplements reduce demyelination in the cuprizone model. PLoS ONE. 2011;6:e26262 pubmed publisher
    ..We investigated the effect of dietary vitamin D3 content on de/remyelination in the cuprizone model, which is a well established toxic model of demyelination, with no associated lymphocyte infiltration...
  46. Plant S, Arnett H, Ting J. Astroglial-derived lymphotoxin-alpha exacerbates inflammation and demyelination, but not remyelination. Glia. 2005;49:1-14 pubmed
    ..demyelination but, more importantly, has demonstrated a novel role for TNFalpha in reparative remyelination in a cuprizone-induced demyelination model. This may explain the worsening of symptoms experienced by MS patients...
  47. Irvine K, Blakemore W. Age increases axon loss associated with primary demyelination in cuprizone-induced demyelination in C57BL/6 mice. J Neuroimmunol. 2006;175:69-76 pubmed
    ..with the areas undergoing demyelination in young adult (8-10 weeks) and aged (6-7 months) C57BL/6 mice in cuprizone intoxication; a widely used model of demyelination...
  48. Irvine K, Blakemore W. Remyelination protects axons from demyelination-associated axon degeneration. Brain. 2008;131:1464-77 pubmed publisher
    ..Remyelination was inhibited by exposing the brain to 40 Gy of X-irradiation prior to cuprizone intoxication and this resulted in a significant increase in the extent of axonal degeneration and loss compared ..
  49. Chandran P, Upadhyay J, Markosyan S, Lisowski A, Buck W, Chin C, et al. Magnetic resonance imaging and histological evidence for the blockade of cuprizone-induced demyelination in C57BL/6 mice. Neuroscience. 2012;202:446-53 pubmed publisher
    ..challenge the integrity of the white matter is the chronic administration of the copper chelator, cuprizone. In the present study, C57BL/6 mice were given 0...
  50. Chen L, Li Z, Ping M, Li R, Liu J, Xie X, et al. Regulation of Olig2 during astroglial differentiation in the subventricular zone of a cuprizone-induced demyelination mouse model. Neuroscience. 2012;221:96-107 pubmed publisher
    ..To determine the functional role of Olig2 in regulating astroglial differentiation in the mouse SVZ, we used the cuprizone mouse model to investigate demyelination...
  51. Arnett H, Fancy S, Alberta J, Zhao C, Plant S, Kaing S, et al. bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS. Science. 2004;306:2111-5 pubmed
    ..Specifically, we demonstrate a genetic requirement for Olig1 in repairing the types of lesions that occur in patients with multiple sclerosis. ..
  52. Adamo A, Paez P, Escobar Cabrera O, Wolfson M, Franco P, Pasquini J, et al. Remyelination after cuprizone-induced demyelination in the rat is stimulated by apotransferrin. Exp Neurol. 2006;198:519-29 pubmed
    Twenty-one-day-old Wistar rats were fed a diet containing 0.6% cuprizone for 2 weeks. Studies carried out after withdrawal of cuprizone showed histological evidences of marked demyelination in the corpus callosum...
  53. Binder M, Cate H, Prieto A, Kemper D, Butzkueven H, Gresle M, et al. Gas6 deficiency increases oligodendrocyte loss and microglial activation in response to cuprizone-induced demyelination. J Neurosci. 2008;28:5195-206 pubmed publisher
    ..family and of their principle cognate ligand, Gas6 (growth arrest gene 6), in modulating the phenotype of the cuprizone model of demyelination...