Clemastine and metformin extend the window of NMDA receptor surface expression in ageing oligodendrocyte precursor cells

In the central nervous system, oligodendrocyte precursor cells (OPCs) proliferate and differentiate into myelinating oligodendrocytes throughout life, allowing for ongoing myelination and myelin repair. With age, differentiation efficacy decreases and myelin repair fails; therefore, recent therapeut...

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Published in:Scientific reports 2024-02, Vol.14 (1), p.4091-4091, Article 4091
Main Authors: Kamen, Yasmine, Evans, Kimberley Anne, Sitnikov, Sergey, Spitzer, Sonia Olivia, de Faria, Omar, Yucel, Mert, Káradóttir, Ragnhildur Thóra
Format: Article
Language:English
Subjects:
631/378/2586
631/378/2596/1705
631/378/2611
Age
Aging
Cell differentiation
Central nervous system
Channel gating
Drinking water
Glial stem cells
Glutamate receptors
Glutamic acid receptors (ionotropic)
Humanities and Social Sciences
Ion channels
Metformin
multidisciplinary
Myelination
N-Methyl-D-aspartic acid receptors
Nervous system
Oligodendrocytes
Science
Science (multidisciplinary)
Voltage
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Summary:In the central nervous system, oligodendrocyte precursor cells (OPCs) proliferate and differentiate into myelinating oligodendrocytes throughout life, allowing for ongoing myelination and myelin repair. With age, differentiation efficacy decreases and myelin repair fails; therefore, recent therapeutic efforts have focused on enhancing differentiation. Many cues are thought to regulate OPC differentiation, including neuronal activity, which OPCs can sense and respond to via their voltage-gated ion channels and glutamate receptors. However, OPCs’ density of voltage-gated ion channels and glutamate receptors differs with age and brain region, and correlates with their proliferation and differentiation potential, suggesting that OPCs exist in different functional cell states, and that age-associated states might underlie remyelination failure. Here, we use whole-cell patch-clamp to investigate whether clemastine and metformin, two pro-remyelination compounds, alter OPC membrane properties and promote a specific OPC state. We find that clemastine and metformin extend the window of NMDAR surface expression, promoting an NMDAR-rich OPC state. Our findings highlight a possible mechanism for the pro-remyelinating action of clemastine and metformin, and suggest that OPC states can be modulated as a strategy to promote myelin repair.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-024-53615-x