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Heterogeneity of white matter astrocytes in the human brain

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Abstract

Astrocytes regulate central nervous system development, maintain its homeostasis and orchestrate repair upon injury. Emerging evidence support functional specialization of astroglia, both between and within brain regions. Different subtypes of gray matter astrocytes have been identified, yet molecular and functional diversity of white matter astrocytes remains largely unexplored. Nonetheless, their important and diverse roles in maintaining white matter integrity and function are well recognized. Compelling evidence indicate that impairment of normal astrocytic function and their response to injury contribute to a wide variety of diseases, including white matter disorders. In this review, we highlight our current understanding of astrocyte heterogeneity in the white matter of the mammalian brain and how an interplay between developmental origins and local environmental cues contribute to astroglial diversification. In addition, we discuss whether, and if so, how, heterogeneous astrocytes could contribute to white matter function in health and disease and focus on the sparse human research data available. We highlight four leukodystrophies primarily due to astrocytic dysfunction, the so-called astrocytopathies. Insight into the role of astroglial heterogeneity in both healthy and diseased white matter may provide new avenues for therapies aimed at promoting repair and restoring normal white matter function.

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Acknowledgements

The study was supported by a grant from ZonMw (TOP 91217006). M.S.v.d.K. is a member of the European Reference Network for Rare Neurological Disorders (ERN-RND), project ID 739510.

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Authors and Affiliations

  1. Department of Pathology, Amsterdam University Medical Centres, Amsterdam Neuroscience, Amsterdam, The Netherlands

    Marianna Bugiani

  2. Department of Paediatrics/Child Neurology, Emma Children’s Hospital, Amsterdam University Medical Centres, Amsterdam Neuroscience, Amsterdam, The Netherlands

    Bonnie C. Plug, Jodie H. K. Man, Marjolein Breur & Marjo S. van der Knaap

  3. Department of Functional Genomics, Centre for Neurogenomics and Cognitive Research, VU University, Amsterdam Neuroscience, Amsterdam, The Netherlands

    Marjo S. van der Knaap

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BCP researched data for the article. MBu, BCP and JHKM discussed the content and wrote the manuscript. MBr designed schematic figures and commented on the manuscript. MSvdK provided the MRI images and MBu the histopathological images. MSvdK and MBu reviewed and edited the manuscript before submission. All the authors agreed on the content of the manuscript.

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Bugiani, M., Plug, B.C., Man, J.H.K. et al. Heterogeneity of white matter astrocytes in the human brain. Acta Neuropathol 143, 159–177 (2022). https://doi.org/10.1007/s00401-021-02391-3

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