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PreprintCited by 5Multiple Sclerosis Research StudiesCell Image Analysis TechniquesDigital Holography and Microscopy

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3d virtual histology reveals pathological alterations of cerebellar granule cells in multiple sclerosis

Open access
Frost, Jakob, Schmitzer, Bernhard, Töpperwien, Mareike, Eckermann, Marina, Franz, Jonas, Stadelmann, Christine, Salditt, Tim·2022·medRxiv
DOI 10.1101/2022.10.07.22280811

Preprint — published as 10.1016/j.neuroscience.2023.04.002 · Paper page

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Abstract

We investigate structural properties of neurons in the granular layer of human cerebellum with respect to their involvement in multiple sclerosis (MS). To this end we analyze data recorded by X-ray phase contrast tomography from tissue samples collected post mortem from a MS and a healthy control group. Using automated segmentation and histogram analysis based on optimal transport theory (OT) we find that the distributions representing nuclear structure in the granular layer move to a more compact nuclear state, i.e. smaller, denser and more heterogeneous nuclei in MS. We have previously made a similar observation for neurons of the dentate gyrus in Alzheimer’s disease, suggesting that more compact structure of neuronal nuclei which we attributed to increased levels of heterochromatin, may possibly represent a more general phenomenon of cellular senescence associated with neurodegeneration.

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Metadata

Authors
Frost, J., Schmitzer, B., Töpperwien, M., Eckermann, M., Franz, J., Stadelmann, C., & Salditt, T.
Affiliations
  • University of Göttingen (DE)
  • European Synchrotron Radiation Facility (FR)
  • Universitätsmedizin Göttingen (DE)
  • Multiscale Bioimaging (DE)
Corresponding author
Salditt, Tim
ORCID
Venue
medRxiv
Publisher
openRxiv
Published
2022-10-10
DOI
10.1101/2022.10.07.22280811
OpenAlex
W4304128492
Cited by
5
References
1
Citations by year
2024: 5
Type
posted content
Language
en
Open access
Licence
cc-by-nc-nd
Locations
  • medRxiv (acceptedVersion, cc-by-nc-nd)
  • Desy publication database (The Deutsches Elektronen-Synchrotron) (submittedVersion, other-oa)
  • Desy Publications Database (Deutsches Elektronen-Synchrotron DESY) (submittedVersion, other-oa)
Funders
Deutsche Forschungsgemeinschaft (CRC 274, EXC 2067, CRC 1456 A03, SFB 1456, CRC1456, EXC 2067‐1, 390729940, EXC 2067/1390729940, 408885537)
Topics
  • Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Cell Image Analysis Techniques
  • Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Digital Holography and Microscopy
Keywords
multiple sclerosis, cerebellar granule cells, granular layer, X-ray phase-contrast tomography, optimal transport, automatic segmentation, heterochromatin, cellular senescence, neurodegeneration

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