Neuroprotective Function of Microglia in the Developing Brain

Overview

Journal Neuronal Signal

Date 2021 Feb 3

PMID 33532089

Citations 12

Authors

Yuki Fujita

Toshihide Yamashita

Affiliations

Soon will be listed here.

Abstract

Microglia are the resident immune cells of the central nervous system and are important for immune processes. Besides their classical roles in pathological conditions, these cells also dynamically interact with neurons and influence their structure and function in physiological conditions. Recent evidence revealed their role in healthy brain homeostasis, including the regulation of neurogenesis, cell survival, and synapse maturation and elimination, especially in the developing brain. In this review, we summarize the current state of knowledge on microglia in brain development, with a focus on their neuroprotective function. We will also discuss how microglial dysfunction may lead to the impairment of brain function, thereby contributing to disease development.

Citing Articles

Impact of neuroinflammation on brain glutamate and dopamine signalling in schizophrenia: an update.

Nayak U, Manikkath J, Arora D, Mudgal J Metab Brain Dis. 2025; 40(2):119.

PMID: 39907868 PMC: 11799129. DOI: 10.1007/s11011-025-01548-3.

BHBA attenuates endoplasmic reticulum stress-dependent neuroinflammation via the gut-brain axis in a mouse model of heat stress.

Sui Y, Feng X, Ma Y, Zou Y, Liu Y, Huang J CNS Neurosci Ther. 2024; 30(7):e14840.

PMID: 38973202 PMC: 11228358. DOI: 10.1111/cns.14840.

How Parkinson's Disease-Linked LRRK2 Mutations Affect Different CNS Cell Types.

Bailey H, Cookson M J Parkinsons Dis. 2024; 14(7):1331-1352.

PMID: 38905056 PMC: 11492021. DOI: 10.3233/JPD-230432.

Activation of Cannabinoid Type 2 Receptor in Microglia Reduces Neuroinflammation through Inhibiting Aerobic Glycolysis to Relieve Hypertension.

Shan R, Zhang Y, Shi Y, Wang X, Wang X, Ma G Biomolecules. 2024; 14(3).

PMID: 38540753 PMC: 10967819. DOI: 10.3390/biom14030333.

The Physio-Pathological Role of Group I Metabotropic Glutamate Receptors Expressed by Microglia in Health and Disease with a Focus on Amyotrophic Lateral Sclerosis.

Balbi M, Bonanno G, Bonifacino T, Milanese M Int J Mol Sci. 2023; 24(6).

PMID: 36982315 PMC: 10048889. DOI: 10.3390/ijms24065240.

References

Wakselman S, Bechade C, Roumier A, Bernard D, Triller A, Bessis A . Developmental neuronal death in hippocampus requires the microglial CD11b integrin and DAP12 immunoreceptor. J Neurosci. 2008; 28(32):8138-43. PMC: 6670768. DOI: 10.1523/JNEUROSCI.1006-08.2008. View

Fujita Y, Nakanishi T, Ueno M, Itohara S, Yamashita T . Netrin-G1 Regulates Microglial Accumulation along Axons and Supports the Survival of Layer V Neurons in the Postnatal Mouse Brain. Cell Rep. 2020; 31(4):107580. DOI: 10.1016/j.celrep.2020.107580. View

Salter M, Beggs S . Sublime microglia: expanding roles for the guardians of the CNS. Cell. 2014; 158(1):15-24. DOI: 10.1016/j.cell.2014.06.008. View

Stevens B, Allen N, Vazquez L, Howell G, Christopherson K, Nouri N . The classical complement cascade mediates CNS synapse elimination. Cell. 2007; 131(6):1164-78. DOI: 10.1016/j.cell.2007.10.036. View

Blank T, Prinz M . Microglia as modulators of cognition and neuropsychiatric disorders. Glia. 2012; 61(1):62-70. DOI: 10.1002/glia.22372. View

Chen S, Tvrdik P, Peden E, Cho S, Wu S, Spangrude G . Hematopoietic origin of pathological grooming in Hoxb8 mutant mice. Cell. 2010; 141(5):775-85. PMC: 2894573. DOI: 10.1016/j.cell.2010.03.055. View

Zhan Y, Paolicelli R, Sforazzini F, Weinhard L, Bolasco G, Pagani F . Deficient neuron-microglia signaling results in impaired functional brain connectivity and social behavior. Nat Neurosci. 2014; 17(3):400-6. DOI: 10.1038/nn.3641. View

Schafer D, Lehrman E, Kautzman A, Koyama R, Mardinly A, Yamasaki R . Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron. 2012; 74(4):691-705. PMC: 3528177. DOI: 10.1016/j.neuron.2012.03.026. View

Hattori Y, Naito Y, Tsugawa Y, Nonaka S, Wake H, Nagasawa T . Transient microglial absence assists postmigratory cortical neurons in proper differentiation. Nat Commun. 2020; 11(1):1631. PMC: 7118101. DOI: 10.1038/s41467-020-15409-3. View

10.

Ueno M, Fujita Y, Tanaka T, Nakamura Y, Kikuta J, Ishii M . Layer V cortical neurons require microglial support for survival during postnatal development. Nat Neurosci. 2013; 16(5):543-51. DOI: 10.1038/nn.3358. View

11.

Li Q, Cheng Z, Zhou L, Darmanis S, Neff N, Okamoto J . Developmental Heterogeneity of Microglia and Brain Myeloid Cells Revealed by Deep Single-Cell RNA Sequencing. Neuron. 2019; 101(2):207-223.e10. PMC: 6336504. DOI: 10.1016/j.neuron.2018.12.006. View

12.

Dugas J, Mandemakers W, Rogers M, Ibrahim A, Daneman R, Barres B . A novel purification method for CNS projection neurons leads to the identification of brain vascular cells as a source of trophic support for corticospinal motor neurons. J Neurosci. 2008; 28(33):8294-305. PMC: 2567869. DOI: 10.1523/JNEUROSCI.2010-08.2008. View

13.

Pont-Lezica L, Beumer W, Colasse S, Drexhage H, Versnel M, Bessis A . Microglia shape corpus callosum axon tract fasciculation: functional impact of prenatal inflammation. Eur J Neurosci. 2014; 39(10):1551-7. DOI: 10.1111/ejn.12508. View

14.

Milligan C, Cunningham T, Levitt P . Differential immunochemical markers reveal the normal distribution of brain macrophages and microglia in the developing rat brain. J Comp Neurol. 1991; 314(1):125-35. DOI: 10.1002/cne.903140112. View

15.

Miyamoto A, Wake H, Ishikawa A, Eto K, Shibata K, Murakoshi H . Microglia contact induces synapse formation in developing somatosensory cortex. Nat Commun. 2016; 7:12540. PMC: 5007295. DOI: 10.1038/ncomms12540. View

16.

Paolicelli R, Bolasco G, Pagani F, Maggi L, Scianni M, Panzanelli P . Synaptic pruning by microglia is necessary for normal brain development. Science. 2011; 333(6048):1456-8. DOI: 10.1126/science.1202529. View

17.

Ling E . Influence of cortisone on amoeboid microglia and microglial cells in the corpus callosum in postnatal rats. J Anat. 1982; 134(Pt 4):705-17. PMC: 1167865. View

18.

Shigemoto-Mogami Y, Hoshikawa K, Goldman J, Sekino Y, Sato K . Microglia enhance neurogenesis and oligodendrogenesis in the early postnatal subventricular zone. J Neurosci. 2014; 34(6):2231-43. PMC: 3913870. DOI: 10.1523/JNEUROSCI.1619-13.2014. View

19.

Frade J, Barde Y . Microglia-derived nerve growth factor causes cell death in the developing retina. Neuron. 1998; 20(1):35-41. DOI: 10.1016/s0896-6273(00)80432-8. View

20.

Hristova M, Cuthill D, Zbarsky V, Acosta-Saltos A, Wallace A, Blight K . Activation and deactivation of periventricular white matter phagocytes during postnatal mouse development. Glia. 2009; 58(1):11-28. DOI: 10.1002/glia.20896. View