{
  "abstract": "Introduction: Parkinson's disease (PD) and aging both disrupt hypothalamic-pituitary-adrenal (HPA) axis function and peripheral immune homeostasis. Whether aging or -synuclein (-syn) pathology alters glucocorticoid (GC) sensitivity of peripheral immune cells has not been investigated. Methods: Using an ex vivo GC sensitivity assay, we assessed the responsiveness of isolated and lipopolysaccharide (LPS)-stimulated splenocytes to the anti-inflammatory effects of increasing doses of corticosterone (CORT) in a wild-type (WT) aging cohort and in a PD -syn transgenic mouse model and respective age-matched controls. Results: Compared with splenocytes from 6-month-old WT mice, splenocytes from 20-month-old WT mice were less sensitive to 0.1 and 0.5 M CORT. Isolated splenocytes from PD vs. control mice were less sensitive to 0.05, 0.1, and 0.5 M CORT specifically at 16 months of age, but not at 6 or 20 months of age. As peripheral immune phenotyping revealed neither differences in HPA axis-related parameters nor in splenic GC receptor expression between PD and age-matched control mice at 6, 16, and 20 months, splenic GC resistance in PD mice at 16 months of age seems to be mediated by downstream GR signaling dysfunction. Conclusion: Together, our results support the hypothesis that -syn pathology accelerates an aging-associated decline in the peripheral sensitivity to anti-inflammatory GCs and may thereby sustain systemic and neuroinflammatory processes in PD.",
  "abstract_shown": true,
  "affiliations": [
    "German Center for Neurodegenerative Diseases (DZNE), Ulm, Germany; Department of Neurology, University Clinic, University of Ulm, Ulm, Germany"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "name": "D. Rombach"
    },
    {
      "name": "V. Bopp"
    },
    {
      "name": "D. Langgartner"
    },
    {
      "name": "V. Grozdanov"
    },
    {
      "name": "J. Kassubek"
    },
    {
      "name": "C. Touma"
    },
    {
      "name": "S. O. Reber"
    },
    {
      "affs": [
        0
      ],
      "name": "K. M. Danzer"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0vxehw52t4gcd.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.27.745197",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.27.745197v1.full",
  "id": "0vxehw52t4gcd",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.27.745197v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7204865089",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.27.745197v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/0vxehw52t4gcd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:13Z",
      "native_id": "10.64898/2026.08.27.745197",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.27.745197v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Dysregulated splenic glucocorticoid sensitivity in aging and an α-synuclein transgenic mouse model of Parkinson's disease",
  "title_text": "Dysregulated splenic glucocorticoid sensitivity in aging and an α-synuclein transgenic mouse model of Parkinson's disease",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:13Z",
  "url": "https://research.draconitic.com/paper/0vxehw52t4gcd",
  "venue": "bioRxiv",
  "versions": []
}