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Accelerated dystrophy and decay of oligodendrocyte precursor cells in the APP/PS1 model of Alzheimer's-like pathology

Accelerated dystrophy and decay of oligodendrocyte precursor cells in the APP/PS1 model of Alzheimer's-like pathology
Accelerated dystrophy and decay of oligodendrocyte precursor cells in the APP/PS1 model of Alzheimer's-like pathology

Myelin disruption is a feature of natural aging and 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. The analysis was performed in the CA1 area of the hippocampus following immunolabeling for NG2 with the nuclear dye Hoescht, to identify OPC and OPC sister cells, a measure of OPC replication. The results indicate a significant decrease in the number of OPCs at 9 months in APP/PS1 mice, compared to age-matched controls, without further decline at 14 months. Also, the number of OPC sister cells declined significantly at 14 months in APP/PS1 mice, which was not observed in age-matched controls. Notably, OPCs also displayed marked morphological changes at 14 months in APP/PS1 mice, characterized by an overall shrinkage of OPC process domains and increased process branching. The results indicate that OPC disruption is a pathological sign in the APP/PS1 mouse model of AD.

Alzheimer’s disease, OPC, hippocampus, myelin, oligodendrocyte progenitor cell
1662-5102
Chacon-De La Rocha, Irene
ba5ebb6a-625d-42de-a3c9-65d2cbdba939
Fryatt, Gemma
afd66d34-31f7-4231-9a7c-50bc283646bd
Rivera, Andrea D.
5affd207-47b0-4759-a6c6-8199965a168c
Verkhratsky, Alexei
5d974726-cbe7-4f6d-b342-3de6e45f3765
Raineteau, Olivier
caf93fe2-42f2-4c33-8bb9-683b2cb5a292
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Butt, Arthur M.
9a4a0e00-94b1-4fa1-bb58-a5f1e2859d9c
Chacon-De La Rocha, Irene
ba5ebb6a-625d-42de-a3c9-65d2cbdba939
Fryatt, Gemma
afd66d34-31f7-4231-9a7c-50bc283646bd
Rivera, Andrea D.
5affd207-47b0-4759-a6c6-8199965a168c
Verkhratsky, Alexei
5d974726-cbe7-4f6d-b342-3de6e45f3765
Raineteau, Olivier
caf93fe2-42f2-4c33-8bb9-683b2cb5a292
Gomez-Nicola, Diego
0680aa66-9dee-47cf-a8d3-e39c988f85b5
Butt, Arthur M.
9a4a0e00-94b1-4fa1-bb58-a5f1e2859d9c

Chacon-De La Rocha, Irene, Fryatt, Gemma, Rivera, Andrea D., Verkhratsky, Alexei, Raineteau, Olivier, Gomez-Nicola, Diego and Butt, Arthur M. (2020) Accelerated dystrophy and decay of oligodendrocyte precursor cells in the APP/PS1 model of Alzheimer's-like pathology. Frontiers in Cellular Neuroscience, 14, [575082]. (doi:10.3389/fncel.2020.575082).

Record type: Article

Abstract

Myelin disruption is a feature of natural aging and 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. The analysis was performed in the CA1 area of the hippocampus following immunolabeling for NG2 with the nuclear dye Hoescht, to identify OPC and OPC sister cells, a measure of OPC replication. The results indicate a significant decrease in the number of OPCs at 9 months in APP/PS1 mice, compared to age-matched controls, without further decline at 14 months. Also, the number of OPC sister cells declined significantly at 14 months in APP/PS1 mice, which was not observed in age-matched controls. Notably, OPCs also displayed marked morphological changes at 14 months in APP/PS1 mice, characterized by an overall shrinkage of OPC process domains and increased process branching. The results indicate that OPC disruption is a pathological sign in the APP/PS1 mouse model of AD.

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575082 Butt Manuscript 2 - Accepted Manuscript
Available under License Creative Commons Attribution.
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More information

Accepted/In Press date: 22 October 2020
Published date: 3 December 2020
Additional Information: Copyright © 2020 Chacon-De-La-Rocha, Fryatt, Rivera, Verkhratsky, Raineteau, Gomez-Nicola and Butt.
Keywords: Alzheimer’s disease, OPC, hippocampus, myelin, oligodendrocyte progenitor cell

Identifiers

Local EPrints ID: 444547
URI: http://eprints.soton.ac.uk/id/eprint/444547
ISSN: 1662-5102
PURE UUID: dbced095-4e69-4c75-bd87-c74fb089eac3
ORCID for Diego Gomez-Nicola: ORCID iD orcid.org/0000-0002-5316-2682

Catalogue record

Date deposited: 23 Oct 2020 16:33
Last modified: 17 Mar 2024 06:01

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Contributors

Author: Irene Chacon-De La Rocha
Author: Gemma Fryatt
Author: Andrea D. Rivera
Author: Alexei Verkhratsky
Author: Olivier Raineteau
Author: Arthur M. Butt

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