{
  "abstract": "Age is a major determinant of demyelination and remyelination capacity. Here, we investigated age-dependent brain responses to acute cuprizone exposure in female C57BL/6 mice using longitudinal multimodal Magnetic resonance imaging (MRI) and histological analyses. Our aim was to determine whether any brain region in very old animals remains susceptible to cuprizone-induced pathology. Adult (6-month-old) and aged (18-month-old) mice received 0.2% cuprizone in the diet for 5 weeks, followed by 4 weeks of recovery on normal chow, with in vivo MRI performed at baseline, during intoxication, and throughout recovery. Magnetization transfer ratio (MTR) and T2-weighted signal were used as MRI surrogates of myelin integrity and neuroinflammation, respectively, whereas T1-weighted signal was assessed as a potential marker sensitive to oxidative stress. In adult mice, cuprizone induced robust and region-specific pathology, including reduced MTR and increased T2-weighted signal in the corpus callosum, accompanied by microgliosis, astrocytosis, and increased APP-positive dystrophic neurites. These abnormalities showed only partial recovery following cuprizone withdrawal. In contrast, cuprizone elicited little or no detectable change in these forebrain white-matter regions and in other brain areas in aged mice. However, the cerebellar nuclei remained susceptible at both ages, exhibiting persistent MTR decreases and T2-weighted signal increases, corroborated by histological evidence of demyelination and gliosis. T1-weighted signal increased broadly in adult, but not in aged, mice during intoxication, consistent with cuprizone-associated oxidative stress. Together, these findings demonstrate pronounced age- and region-dependent effects of cuprizone and identify the cerebellar nuclei as a sensitive target of demyelination across the lifespan. Moreover, the non-invasive nature of MRI enables efficient assessment of regional differences over time.",
  "abstract_shown": true,
  "affiliations": [
    "Neurosciences, Novartis Biomedical Research, CH-4056 Basel, Switzerland",
    "Diseases of Aging and Regenerative Medicine, Novartis Biomedical Research, CH-4056 Basel, Switzerland"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Derya R. Shimshek"
    },
    {
      "affs": [
        0
      ],
      "name": "Stefan Zurbruegg"
    },
    {
      "affs": [
        0
      ],
      "name": "Anna Neuhaus"
    },
    {
      "affs": [
        1
      ],
      "name": "Arno Doelemeyer"
    },
    {
      "affs": [
        1
      ],
      "name": "Nicolau Beckmann"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1gd648fw9y66r.bib",
  "cited_by": 0,
  "doi": "10.1016/j.nbas.2026.100171",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13696825/",
  "id": "1gd648fw9y66r",
  "issns": [
    "2589-9589"
  ],
  "landing_url": "https://doi.org/10.1016/j.nbas.2026.100171",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research Article"
    ],
    [
      "openalex",
      "2734|Multiple Sclerosis Research Studies"
    ]
  ],
  "openalex": "W7222812218",
  "pdf_url": "https://europepmc.org/articles/PMC13696825?pdf=render",
  "pmcid": "PMC13696825",
  "pmid": "42936164",
  "published": "2026-10-17",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/1gd648fw9y66r.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:06Z",
      "native_id": "PMC13696825",
      "source": "pmc",
      "url": "https://doi.org/10.1016/j.nbas.2026.100171"
    },
    {
      "first_seen": "2026-10-30T12:22:12Z",
      "native_id": "MED:42936164",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42936164"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2734|Multiple Sclerosis Research Studies",
      "subfield": "general"
    }
  ],
  "title": "Cerebellar nuclei remain vulnerable to cuprizone-induced demyelination in adult and aged mice: A longitudinal multimodal MRI-histology study",
  "title_text": "Cerebellar nuclei remain vulnerable to cuprizone-induced demyelination in adult and aged mice: A longitudinal multimodal MRI-histology study",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:34:05Z",
  "url": "https://research.draconitic.com/paper/1gd648fw9y66r",
  "venue": "Aging Brain",
  "versions": []
}