TY - JOUR
T1 - Heterogeneity of white matter astrocytes in the human brain
AU - Bugiani, Marianna
AU - Plug, Bonnie C.
AU - Man, Jodie H.K.
AU - Breur, Marjolein
AU - van der Knaap, Marjo S.
N1 - Funding Information: 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. Funding Information: 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. Publisher Copyright: © 2021, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2022/2
Y1 - 2022/2
N2 - 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.
AB - 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.
KW - Astrocytes
KW - Astrocytopathy
KW - Heterogeneity
KW - Human brain
KW - Leukodystrophy
KW - White matter
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U2 - https://doi.org/10.1007/s00401-021-02391-3
DO - https://doi.org/10.1007/s00401-021-02391-3
M3 - Review article
C2 - 34878591
SN - 0001-6322
VL - 143
SP - 159
EP - 177
JO - Acta Neuropathologica
JF - Acta Neuropathologica
IS - 2
ER -