Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2018 May 1

PMID 29706957

Citations 244

Authors

Kathryn M Lenz

Lars H Nelson

Affiliations

Soon will be listed here.

Abstract

Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer's disease, traumatic brain and spinal cord injury, and brain cancers. In contrast, it is only recently becoming clear that innate immune cells, primarily brain resident macrophages called microglia, are also key regulators of brain development. This review summarizes the current state of knowledge regarding microglia in brain development, with particular emphasis on how microglia during development are distinct from microglia later in life. We also summarize the effects of early life perturbations on microglia function in the developing brain, the role that biological sex plays in microglia function, and the potential role that microglia may play in developmental brain disorders. Finally, given how new the field of developmental neuroimmunology is, we highlight what has yet to be learned about how innate immune cells shape the development of brain and behavior.

Citing Articles

Fully automated radiosynthesis of [F]FCPPC for imaging microglia with PET.

Roy P, Guo Y, Muzik O, Woodcock E, Jiang H Am J Nucl Med Mol Imaging. 2025; 14(6):351-356.

PMID: 39840376 PMC: 11744358. DOI: 10.62347/QFGP5253.

A comprehensive neuroimaging review of the primary and metastatic brain tumors treated with immunotherapy: current status, and the application of advanced imaging approaches and artificial intelligence.

Liu X, Chen H, Tan G, Zhong L, Jiang H, Smith S Front Immunol. 2024; 15():1496627.

PMID: 39669560 PMC: 11634813. DOI: 10.3389/fimmu.2024.1496627.

The amino acid metabolism pathway of peripheral T lymphocytes and ketamine-induced schizophrenia-like phenotype.

Wang P, Jiang L, Hu J, Jiang Z, Zhang Y, Chen C J Psychiatry Neurosci. 2024; 49(6):E413-E426.

PMID: 39626901 PMC: 11633891. DOI: 10.1503/jpn-240038.

Dispensable regulation of brain development and myelination by the immune-related protein Serpina3n.

Zhu M, Wang Y, Park J, Titus A, Guo F J Neurochem. 2024; 169(2):e16250.

PMID: 39450611 PMC: 11810613. DOI: 10.1111/jnc.16250.

Transient CSF1R inhibition ameliorates behavioral deficits in Cntnap2 knockout and valproic acid-exposed mouse models of autism.

Meng J, Pan P, Guo G, Chen A, Meng X, Liu H J Neuroinflammation. 2024; 21(1):262.

PMID: 39425203 PMC: 11487716. DOI: 10.1186/s12974-024-03259-5.

References

George F, Ojeda S . Changes in aromatase activity in the rat brain during embryonic, neonatal, and infantile development. Endocrinology. 1982; 111(2):522-9. DOI: 10.1210/endo-111-2-522. View

Kochunov P, Coyle T, Rowland L, Jahanshad N, Thompson P, Kelly S . Association of White Matter With Core Cognitive Deficits in Patients With Schizophrenia. JAMA Psychiatry. 2017; 74(9):958-966. PMC: 5710230. DOI: 10.1001/jamapsychiatry.2017.2228. View

Kim I, Mlsna L, Yoon S, Le B, Yu S, Xu D . A postnatal peak in microglial development in the mouse hippocampus is correlated with heightened sensitivity to seizure triggers. Brain Behav. 2016; 5(12):e00403. PMC: 4714636. DOI: 10.1002/brb3.403. View

Jost A, Vigier B, Prepin J, Perchellet J . Studies on sex differentiation in mammals. Recent Prog Horm Res. 1973; 29:1-41. DOI: 10.1016/b978-0-12-571129-6.50004-x. View

Pinto D, Delaby E, Merico D, Barbosa M, Merikangas A, Klei L . Convergence of genes and cellular pathways dysregulated in autism spectrum disorders. Am J Hum Genet. 2014; 94(5):677-94. PMC: 4067558. DOI: 10.1016/j.ajhg.2014.03.018. View

Brown A, Sourander A, Hinkka-Yli-Salomaki S, McKeague I, Sundvall J, Surcel H . Elevated maternal C-reactive protein and autism in a national birth cohort. Mol Psychiatry. 2013; 19(2):259-64. PMC: 3633612. DOI: 10.1038/mp.2012.197. View

Lee B, Magnusson C, Gardner R, Blomstrom A, Newschaffer C, Burstyn I . Maternal hospitalization with infection during pregnancy and risk of autism spectrum disorders. Brain Behav Immun. 2014; 44:100-5. PMC: 4418173. DOI: 10.1016/j.bbi.2014.09.001. View

VanRyzin J, Yu S, Perez-Pouchoulen M, McCarthy M . Temporary Depletion of Microglia during the Early Postnatal Period Induces Lasting Sex-Dependent and Sex-Independent Effects on Behavior in Rats. eNeuro. 2016; 3(6). PMC: 5144556. DOI: 10.1523/ENEURO.0297-16.2016. View

Notter T, Coughlin J, Gschwind T, Weber-Stadlbauer U, Wang Y, Kassiou M . Translational evaluation of translocator protein as a marker of neuroinflammation in schizophrenia. Mol Psychiatry. 2017; 23(2):323-334. DOI: 10.1038/mp.2016.248. View

10.

Sanders S, He X, Willsey A, Ercan-Sencicek A, Samocha K, Cicek A . Insights into Autism Spectrum Disorder Genomic Architecture and Biology from 71 Risk Loci. Neuron. 2015; 87(6):1215-1233. PMC: 4624267. DOI: 10.1016/j.neuron.2015.09.016. View

11.

Buttgereit A, Lelios I, Yu X, Vrohlings M, Krakoski N, Gautier E . Sall1 is a transcriptional regulator defining microglia identity and function. Nat Immunol. 2016; 17(12):1397-1406. DOI: 10.1038/ni.3585. View

12.

Distler M, Opal M, Dulawa S, Palmer A . Assessment of behaviors modeling aspects of schizophrenia in Csmd1 mutant mice. PLoS One. 2013; 7(12):e51235. PMC: 3524225. DOI: 10.1371/journal.pone.0051235. View

13.

Kraus D, Elliott G, Chute H, Horan T, Pfenninger K, Sanford S . CSMD1 is a novel multiple domain complement-regulatory protein highly expressed in the central nervous system and epithelial tissues. J Immunol. 2006; 176(7):4419-30. DOI: 10.4049/jimmunol.176.7.4419. View

14.

Alliot F, Godin I, Pessac B . Microglia derive from progenitors, originating from the yolk sac, and which proliferate in the brain. Brain Res Dev Brain Res. 1999; 117(2):145-52. DOI: 10.1016/s0165-3806(99)00113-3. View

15.

Parkhurst C, Yang G, Ninan I, Savas J, Yates 3rd J, Lafaille J . Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell. 2013; 155(7):1596-609. PMC: 4033691. DOI: 10.1016/j.cell.2013.11.030. View

16.

Amateau S, McCarthy M . A novel mechanism of dendritic spine plasticity involving estradiol induction of prostaglandin-E2. J Neurosci. 2002; 22(19):8586-96. PMC: 6757802. View

17.

Andjelkovic A, Nikolic B, Pachter J, Zecevic N . Macrophages/microglial cells in human central nervous system during development: an immunohistochemical study. Brain Res. 1998; 814(1-2):13-25. DOI: 10.1016/s0006-8993(98)00830-0. View

18.

Wright C, Burks S, McCarthy M . Identification of prostaglandin E2 receptors mediating perinatal masculinization of adult sex behavior and neuroanatomical correlates. Dev Neurobiol. 2008; 68(12):1406-19. PMC: 2725403. DOI: 10.1002/dneu.20665. View

19.

Dong Y, Benveniste E . Immune function of astrocytes. Glia. 2001; 36(2):180-90. DOI: 10.1002/glia.1107. View

20.

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