ArticlePloS one2015
Thymic Atrophy and Apoptosis of CD4+CD8+ Thymocytes in the Cuprizone Model of Multiple Sclerosis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Within and beyond the tumor: Mechanisms of glioblastoma-induced immunosuppression.Neuro-oncology advances · 2025Review
- Dynamic Transcriptomic and Cellular Remodeling Underlie Cuprizone-Induced Demyelination and Endogenous Repair in the CNS.Antioxidants (Basel, Switzerland) · 2025Article
- Neural regulation of the thymus: past, current, and future perspectives.Frontiers in immunology · 2025Review
- Potential therapeutic effects of ibudilast and retinoic acid against cuprizone-induced behavioral and biochemical changes in mouse brain.Frontiers in molecular neuroscience · 2025Article
- Aging-dependent immunological changes in multiple sclerosis.Frontiers in immunology · 2025Article
- Olig2Journal of Zhejiang University. Science. B · 2024Article
- Oligodendrocyte death and myelin loss in the cuprizone model: an updated overview of the intrinsic and extrinsic causes of cuprizone demyelination.Molecular neurodegeneration · 2022Review
- Animal models to investigate the effects of inflammation on remyelination in multiple sclerosis.Frontiers in molecular neuroscience · 2022Review
- Proteomics of Multiple Sclerosis: Inherent Issues in Defining the Pathoetiology and Identifying (Early) Biomarkers.International journal of molecular sciences · 2021Review
- Pre-clinical and Clinical Implications of "Inside-Out" vs. "Outside-In" Paradigms in Multiple Sclerosis Etiopathogenesis.Frontiers in cellular neuroscience · 2020Review
- CD8 T-cell Recruitment Into the Central Nervous System of Cuprizone-Fed Mice: Relevance to Modeling the Etiology of Multiple Sclerosis.Frontiers in cellular neuroscience · 2020Article
- Absence of miRNA-146a Differentially Alters Microglia Function and Proteome.Frontiers in immunology · 2020Article
- Revisiting the Pathoetiology of Multiple Sclerosis: Has the Tail Been Wagging the Mouse?Frontiers in immunology · 2020Review
- Article
- Correlation Between Smoking and Passive Smoking with Multiple Sclerosis and the Underlying Molecular Mechanisms.Medical science monitor : international medical journal of experimental and clinical research · 2019Review
- Transgenic Exosomes for Thymus Regeneration.Frontiers in immunology · 2019Article
- Experimental Demyelination and Axonal Loss Are Reduced in MicroRNA-146a Deficient Mice.Frontiers in immunology · 2018Article
- Immune Thymic Profile of the MOG-Induced Experimental Autoimmune Encephalomyelitis Mouse Model.Frontiers in immunology · 2018Article
- Strain differences in thymic atrophy in rats immunized for EAE correlate with the clinical outcome of immunization.PloS one · 2018Article
- Zinc is a determinant of the cytotoxicity of Ziram, a dithiocarbamate fungicide, in rat thymic lymphocytes: possible environmental risks.Toxicology research · 2017Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous studies on the degenerative animal model of multiple sclerosis suggested that the copper-chelator cuprizone might directly suppress T-cell functions. Peripheral T-cell function in the cuprizone model has already been explored; therefore, in the present study, we investigated, for the first time, how cuprizone feeding affects the thymus, the organ of T-cell maturation and selection. We found that even one week of cuprizone treatment induced significant thymic atrophy, affecting the cortex over the medulla. Fluorescent microscopy and flow-cytometric analyses of thymi from cuprizone- and vehicle-treated mice indicated that eradication of the cluster of the differentiation-4 (CD4)-CD8 double-positive T-cell subset was behind the substantial cell loss. This result was confirmed with CD3-CD4-CD8 triple-staining experiments. Ultrastructurally, we observed degraded as well as enlarged mitochondria, myelin-bodies, large lipid droplets, and large lysosomes in the thymi of cuprizone-treated mice. Some of these features were similar to those in physiological and steroid-induced accelerated aging. According to our results, apoptosis was mainly of mitochondrial origin mediated by both caspase-3- and apoptosis inducing factor-mediated mechanisms. Additionally, mitogen activated protein kinase activation and increased pro-apoptotic B cell lymphoma-2 family protein expression were the major underlying processes. Our results do not indicate a functional relationship between cuprizone-induced thymus involution and the absence of inflammatory responses or the selective demyelination observed in the cuprizone model. On the other hand, due to the reversible nature of cuprizone's deleterious effects, the cuprizone model could be valuable in studying thymus regeneration as well as remyelination processes.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.