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Cited by 52Neurogenesis and neuroplasticity mechanismsAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Accelerated Dystrophy and Decay of Oligodendrocyte Precursor Cells in the APP/PS1 Model of Alzheimer’s-Like Pathology

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Chacon-De-La-Rocha, Irene, Fryatt, Gemma, Rivera, Andrea D., Verkhratsky, Alexei, Raineteau, Olivier, Gomez-Nicola, Diego, Butt, Arthur M.·2020·Frontiers in Cellular Neuroscience
DOI 10.3389/fncel.2020.575082PMC PMC7744306

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Abstract

Abstract Myelin disruption is a feature of natural aging and of Alzheimer’s disease (AD). In the CNS, myelin is produced by oligodendrocytes, which are generated throughout life by oligodendrocyte progenitor cells (OPCs). Here, we examined age-related changes in OPCs in APP/PS1 mice, a model for AD-like pathology, compared with non-transgenic (Tg) age-matched controls. Analysis was performed in the CA1 area of the hippocampus following immunolabelling for NG2 with the nuclear dye Hoescht, to identify OPC and OPC sister cells, a measure of OPC replication, together with Gpr17 and Olig2 for oligodendrocytes and myelin basic protein (MBP) immunostaining as a measure of myelination. The results indicate a decrease in the number of OPCs between 9 and 14 months in natural ageing and this occurred earlier at 9 months in APP/PS1 mice, without further decline at 14 months. The number of OPC sister cells was unaltered in natural aging, but declined significantly at 14-months in APP/PS1 mice. The number of GPR17+ and Olig2+ oligodendrocytes was not altered in APP/PS1, whereas MBP immunostaining increased between 9 and 14 months in natural ageing, but not in APP/PS1 mice. Notably, OPCs displayed marked morphological changes at 14 months in APP/PS1 mice, characterized by an overall shrinkage of OPC process domains and increased process branching, characteristic of reactive pathological changes. The results indicate that OPC and myelin disruption are pathological signs in the APP/PS1 mouse model of AD.

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  • The early epoch features losses of oligodendrocytes and a dramatic increase in OPC differentiation and remyelination factors that may represent a compensatory response like that seen in models of oligodendrocyte loss.

    “This epoch also features losses of oligodendrocytes and a dramatic increase in OPC differentiation and remyelination factors that may represent a compensatory response like that seen in models of oligodendrocyte loss86,87.”

    From Integrated multimodal cell atlas of Alzheimer’s disease (2024) · cites this paper as [86]

    The Abstract reports an early decrease in oligodendrocyte precursor cells (OPCs) in APP/PS1 mice, and the Discussion reports reduced myelin staining. Neither passage establishes a loss of mature oligodendrocytes, and the paper does not report a dramatic increase in OPC differentiation or remyelination factors as a compensatory response. No page numbers are available in our copy. (LLM, conf=0.79)

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Authors
Chacon-De-La-Rocha, I., Fryatt, G., Rivera, A. D., Verkhratsky, A., Raineteau, O., Gomez-Nicola, D., & Butt, A. M.
Affiliations
  • Southampton General Hospital (GB)
  • University of Portsmouth (GB)
  • University of Manchester (GB)
  • Lyon 1 Université (FR)
Corresponding author
Butt, Arthur M.
ORCID
Venue
Frontiers in Cellular Neuroscience
Publisher
Frontiers Media SA
Published
2020-12-03
Volume
14
Pages
575082-575082
ISSN
1662-5102 (ISSN-L)
DOI
10.3389/fncel.2020.575082
PMC
PMC7744306
OpenAlex
W3108008464
Cited by
52
References
58
Citations by year
2026: 5 · 2025: 9 · 2024: 11 · 2023: 12 · 2022: 9 · 2021: 6
FWCI
2.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Cellular Neuroscience (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion, other-oa)
  • ePrints Soton (University of Southampton) (submittedVersion)
  • HAL (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Biotechnology and Biological Sciences Research Council
  • Medical Research Council
  • Alzheimer’s Research UK
Topics
  • Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
oligodendrocyte precursor cells, APP/PS1 mice, Alzheimer's disease, myelin damage, NG2, hippocampal CA1, aging

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