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Microglial contribution to the pathology of neurodevelopmental disorders in humans

Microglial contribution to the pathology of neurodevelopmental disorders in humans
Microglial contribution to the pathology of neurodevelopmental disorders in humans

Microglia are the brain's resident macrophages, which guide various developmental processes crucial for brain maturation, activity, and plasticity. Microglial progenitors enter the telencephalic wall by the 4th postconceptional week and colonise the fetal brain in a manner that spatiotemporally tracks key neurodevelopmental processes in humans. However, much of what we know about how microglia shape neurodevelopment comes from rodent studies. Multiple differences exist between human and rodent microglia warranting further focus on the human condition, particularly as microglia are emerging as critically involved in the pathological signature of various cognitive and neurodevelopmental disorders. In this article, we review the evidence supporting microglial involvement in basic neurodevelopmental processes by focusing on the human species. We next concur on the neuropathological evidence demonstrating whether and how microglia contribute to the aetiology of two neurodevelopmental disorders: autism spectrum conditions and schizophrenia. Next, we highlight how recent technologies have revolutionised our understanding of microglial biology with a focus on how these tools can help us elucidate at unprecedented resolution the links between microglia and neurodevelopmental disorders. We conclude by reviewing which current treatment approaches have shown most promise towards targeting microglia in neurodevelopmental disorders and suggest novel avenues for future consideration.

Humans, Microglia/pathology, Neurodevelopmental Disorders/pathology, Autism Spectrum Disorder, Macrophages/pathology, Neuropathology, Brain/pathology
0001-6322
663-683
Matuleviciute, Rugile
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Akinluyi, Elizabeth T.
2da8d3b8-0bba-4820-aaf8-0bb0dc0fe388
Muntslag, Tim A.O.
a259a619-8e56-44b7-8b03-c5342d6c14b8
Dewing, Jennifer M.
868fbf01-7b6e-499f-abf9-47409278373f
Long, Katherine R.
664bd115-4dd9-484d-8aeb-b9d09b0075ed
Vernon, Anthony C.
f26fb8d7-41a7-4db6-9377-516df652395e
Tremblay, Marie-Eve
5b3c67fa-b651-455a-a7f7-f602dfe993fd
Menassa, David A.
97a6a9e5-ef88-45a3-a6e4-f54e9775f533
Matuleviciute, Rugile
f50fbd03-be3c-4685-bef8-7fa4762943bb
Akinluyi, Elizabeth T.
2da8d3b8-0bba-4820-aaf8-0bb0dc0fe388
Muntslag, Tim A.O.
a259a619-8e56-44b7-8b03-c5342d6c14b8
Dewing, Jennifer M.
868fbf01-7b6e-499f-abf9-47409278373f
Long, Katherine R.
664bd115-4dd9-484d-8aeb-b9d09b0075ed
Vernon, Anthony C.
f26fb8d7-41a7-4db6-9377-516df652395e
Tremblay, Marie-Eve
5b3c67fa-b651-455a-a7f7-f602dfe993fd
Menassa, David A.
97a6a9e5-ef88-45a3-a6e4-f54e9775f533

Matuleviciute, Rugile, Akinluyi, Elizabeth T., Muntslag, Tim A.O., Dewing, Jennifer M., Long, Katherine R., Vernon, Anthony C., Tremblay, Marie-Eve and Menassa, David A. (2023) Microglial contribution to the pathology of neurodevelopmental disorders in humans. Acta Neuropathologica, 146 (5), 663-683. (doi:10.1007/s00401-023-02629-2).

Record type: Review

Abstract

Microglia are the brain's resident macrophages, which guide various developmental processes crucial for brain maturation, activity, and plasticity. Microglial progenitors enter the telencephalic wall by the 4th postconceptional week and colonise the fetal brain in a manner that spatiotemporally tracks key neurodevelopmental processes in humans. However, much of what we know about how microglia shape neurodevelopment comes from rodent studies. Multiple differences exist between human and rodent microglia warranting further focus on the human condition, particularly as microglia are emerging as critically involved in the pathological signature of various cognitive and neurodevelopmental disorders. In this article, we review the evidence supporting microglial involvement in basic neurodevelopmental processes by focusing on the human species. We next concur on the neuropathological evidence demonstrating whether and how microglia contribute to the aetiology of two neurodevelopmental disorders: autism spectrum conditions and schizophrenia. Next, we highlight how recent technologies have revolutionised our understanding of microglial biology with a focus on how these tools can help us elucidate at unprecedented resolution the links between microglia and neurodevelopmental disorders. We conclude by reviewing which current treatment approaches have shown most promise towards targeting microglia in neurodevelopmental disorders and suggest novel avenues for future consideration.

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s00401-023-02629-2 - Version of Record
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Accepted/In Press date: 26 August 2023
e-pub ahead of print date: 1 September 2023
Published date: November 2023
Keywords: Humans, Microglia/pathology, Neurodevelopmental Disorders/pathology, Autism Spectrum Disorder, Macrophages/pathology, Neuropathology, Brain/pathology

Identifiers

Local EPrints ID: 500361
URI: http://eprints.soton.ac.uk/id/eprint/500361
ISSN: 0001-6322
PURE UUID: c8b8048e-1904-40d6-b347-894606cb3eb1

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Date deposited: 28 Apr 2025 16:38
Last modified: 21 Aug 2025 04:22

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Contributors

Author: Rugile Matuleviciute
Author: Elizabeth T. Akinluyi
Author: Tim A.O. Muntslag
Author: Jennifer M. Dewing
Author: Katherine R. Long
Author: Anthony C. Vernon
Author: Marie-Eve Tremblay
Author: David A. Menassa

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