Astrocyte Activation Persists after Recovery of Myelin and Motor Deficits in the Cuprizone Model: a Longitudinal PET and CNS Tissue Analysis Study.
Overview
- Department of Molecular Neurobiology, Groningen Institute of Evolutionary Life Science (GELIFES), University of Groningen,Groningen, The Netherlands
- Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen,Groningen, The Netherlands
- Applied Research Center, Van Hall Larenstein University of Applied Science,Leeuwarden, The Netherlands
Abstract
Purpose: The cuprizone (CPZ) mouse model for multiple sclerosis enables researchers to investigate the underlying mechanisms of demyelination and remyelination, as well as the effect of therapeutic interventions thereon. Over the last five decades, research revealed detailed analyses of brain tissue derived from CPZ-fed animals at different times of de- and re-myelination. Yet, longitudinal analysis of the effects of a CPZ diet on locomotor performance, myelination and neuroinflammation over a two-month recovery period are still unexplored.
Procedures: In this study, we comprehensively examined behavioural and neuropathological changes in the CPZ mouse model for a follow-up period of two months. We combined a longitudinal PET imaging approach with a more traditional approach of obtaining tissue and performing immunohistochemistry and behavioural tests in cohorts.
Results: We found that mice fed with 0.2% CPZ for 5 weeks showed transient motor deficits which recovered quickly after cuprizone was removed from the diet. Similarly, remyelination also promptly restored myelin content after CPZ toxic insult, as seen by PET imaging with [11C]MeDAS and myelin histological staining. Remarkably, five weeks of CPZ feeding led to persistent glial activation, especially in the corpus callosum, for at least two months. This effect was measured both with [11C]PK11195 PET and with immunohistochemical staining for microglia and astrocytes.
Conclusions: Taken together, this longitudinal study reveals that a five-week CPZ diet leads to transient motor and loss of myelin, which recover quickly after CPZ is removed. In contrast, neuroinflammation persists for at least two months following exposure and is mainly driven by astrocyte activation. The study warrants deeper analysis of the sustained neuroinflammatory response in the context of demyelinating diseases.
Supplementary Information: The online version contains supplementary material available at 10.1007/
Reproduced under the paper's license (CC BY), from the paper cited above.
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Version 1, 30 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 8 authors, 9 keywords, 14 MeSH terms, 1 funder, 48 references.
Cite
This paper
Pegoretti, V., Boerema, A. S., Sijbesma, J. W. A., Dietz, L. E. R., Alberts, N., Douwenga, W., Eisel, U. L. M., & de Vries, E. F. J. (2026). Astrocyte Activation Persists after Recovery of Myelin and Motor Deficits in the Cuprizone Model: a Longitudinal PET and CNS Tissue Analysis Study. Molecular imaging and biology, 28(3), 457-469. https://
BibTeX
@article{pegoretti2026as
author = {Pegoretti, V. and Boerema, A. S. and Sijbesma, J. W. A. and Dietz, L. E. R. and Alberts, N. and Douwenga, W. and Eisel, U. L. M. and de Vries, E. F. J.},
title = {{Astrocyte Activation Persists after Recovery of Myelin and Motor Deficits in the Cuprizone Model: a Longitudinal PET and CNS Tissue Analysis Study}},
journal = {Molecular imaging and biology},
year = {2026},
month = mar,
volume = {28},
number = {3},
pages = {457--469},
publisher = {Springer Science+Business Media},
issn = {1536-1632},
doi = {10.1007/
url = {https://
pmid = {41874822},
pmcid = {PMC13337915}
}
RIS
TY - JOUR
AU - Pegoretti, V.
AU - Boerema, A. S.
AU - Sijbesma, J. W. A.
AU - Dietz, L. E. R.
AU - Alberts, N.
AU - Douwenga, W.
AU - Eisel, U. L. M.
AU - de Vries, E. F. J.
TI - Astrocyte Activation Persists after Recovery of Myelin and Motor Deficits in the Cuprizone Model: a Longitudinal PET and CNS Tissue Analysis Study
T2 - Molecular imaging and biology
J2 - Mol Imaging Biol
PY - 2026
DA - 2026/
VL - 28
IS - 3
SP - 457
EP - 469
SN - 1536-1632
PB - Springer Science+Business Media
DO - 10.1007/
UR - https://
LA - en
ER -
CSL-JSON
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