Novel Roles for Immune Molecules in Neural Development: Implications for Neurodevelopmental Disorders

Overview

Journal Front Synaptic Neurosci

Date 2011 Mar 23

PMID 21423522

Citations 113

Authors

Paula A Garay

A Kimberley McAllister

Affiliations

Soon will be listed here.

Abstract

Although the brain has classically been considered "immune-privileged", current research suggests an extensive communication between the immune and nervous systems in both health and disease. Recent studies demonstrate that immune molecules are present at the right place and time to modulate the development and function of the healthy and diseased central nervous system (CNS). Indeed, immune molecules play integral roles in the CNS throughout neural development, including affecting neurogenesis, neuronal migration, axon guidance, synapse formation, activity-dependent refinement of circuits, and synaptic plasticity. Moreover, the roles of individual immune molecules in the nervous system may change over development. This review focuses on the effects of immune molecules on neuronal connections in the mammalian central nervous system - specifically the roles for MHCI and its receptors, complement, and cytokines on the function, refinement, and plasticity of geniculate, cortical and hippocampal synapses, and their relationship to neurodevelopmental disorders. These functions for immune molecules during neural development suggest that they could also mediate pathological responses to chronic elevations of cytokines in neurodevelopmental disorders, including autism spectrum disorders (ASD) and schizophrenia.

Citing Articles

Peripheral Blood Monocytes as Biomarkers of Neurodevelopmental Disorders: A Systematic Review and Meta-Analysis.

Ju X, Zhang P, Li Q, Bai Q, Hu B, Xu J Res Child Adolesc Psychopathol. 2025; .

PMID: 40053221 DOI: 10.1007/s10802-025-01303-3.

Autistic traits foster effective curiosity-driven exploration.

Poli F, Koolen M, Velazquez-Vargas C, Ramos-Sanchez J, Meyer M, Mars R PLoS Comput Biol. 2024; 20(10):e1012453.

PMID: 39480751 PMC: 11527316. DOI: 10.1371/journal.pcbi.1012453.

Ulinastatin modulates NLRP3 inflammasome pathway in PTZ-induced epileptic mice: A potential mechanistic insight.

Wang H, Ma Y, Jin D, Yang X, Xu X Heliyon. 2024; 10(19):e38050.

PMID: 39386862 PMC: 11462202. DOI: 10.1016/j.heliyon.2024.e38050.

Prediction of immune molecules activity during burn wound healing among elderly patients: in-silico analyses: experimental research.

Zabihi M, Akhoondian M, Tamimi P, Ghaderi A, Mazhari S, Farhadi B Ann Med Surg (Lond). 2024; 86(7):3972-3983.

PMID: 38989182 PMC: 11230785. DOI: 10.1097/MS9.0000000000002055.

Associations between atypical intracortical myelin content and neuropsychological functions in middle to older aged adults with ASD.

Kohli J, Linke A, Martindale I, Wilkinson M, Kinnear M, Lincoln A Brain Behav. 2024; 14(6):e3594.

PMID: 38849980 PMC: 11161394. DOI: 10.1002/brb3.3594.

References

Lidman O, Olsson T, Piehl F . Expression of nonclassical MHC class I (RT1-U) in certain neuronal populations of the central nervous system. Eur J Neurosci. 1999; 11(12):4468-72. DOI: 10.1046/j.1460-9568.1999.00904.x. View

Meyer U, Nyffeler M, Schwendener S, Knuesel I, Yee B, Feldon J . Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after in utero immune challenge. Neuropsychopharmacology. 2007; 33(2):441-56. DOI: 10.1038/sj.npp.1301413. View

Yang S, Liu Z, Wen L, Qiao H, Zhou W, Zhang Y . Interleukin-1beta enhances NMDA receptor-mediated current but inhibits excitatory synaptic transmission. Brain Res. 2005; 1034(1-2):172-9. DOI: 10.1016/j.brainres.2004.11.018. View

Yee B, Keist R, von Boehmer L, Studer R, Benke D, Hagenbuch N . A schizophrenia-related sensorimotor deficit links alpha 3-containing GABAA receptors to a dopamine hyperfunction. Proc Natl Acad Sci U S A. 2005; 102(47):17154-9. PMC: 1288020. DOI: 10.1073/pnas.0508752102. View

Alboni S, Cervia D, Sugama S, Conti B . Interleukin 18 in the CNS. J Neuroinflammation. 2010; 7:9. PMC: 2830964. DOI: 10.1186/1742-2094-7-9. View

Sperner-Unterweger B . Immunological aetiology of major psychiatric disorders: evidence and therapeutic implications. Drugs. 2005; 65(11):1493-520. DOI: 10.2165/00003495-200565110-00004. View

Fujimaki H, Hikawa N, Nagoya M, Nagata T, Minami M . IFN-gamma induces expression of MHC class I molecules in adult mouse dorsal root ganglion neurones. Neuroreport. 1996; 7(18):2951-5. DOI: 10.1097/00001756-199611250-00030. View

Khan A, Bose C, Yam L, Soloski M, Rupp F . Physiological regulation of the immunological synapse by agrin. Science. 2001; 292(5522):1681-6. DOI: 10.1126/science.1056594. View

Hensch T, Gordon J, Brandon E, McKnight G, Idzerda R, Stryker M . Comparison of plasticity in vivo and in vitro in the developing visual cortex of normal and protein kinase A RIbeta-deficient mice. J Neurosci. 1998; 18(6):2108-17. PMC: 2553093. View

10.

Bryceson Y, Foster J, Kuppusamy S, Herkenham M, Long E . Expression of a killer cell receptor-like gene in plastic regions of the central nervous system. J Neuroimmunol. 2005; 161(1-2):177-82. DOI: 10.1016/j.jneuroim.2004.11.018. View

11.

Perry V, OConnor V . C1q: the perfect complement for a synaptic feast?. Nat Rev Neurosci. 2008; 9(11):807-11. DOI: 10.1038/nrn2394. View

12.

Stefansson H, Ophoff R, Steinberg S, Andreassen O, Cichon S, Rujescu D . Common variants conferring risk of schizophrenia. Nature. 2009; 460(7256):744-7. PMC: 3077530. DOI: 10.1038/nature08186. View

13.

Letellier M, Willson M, Gautheron V, Mariani J, Lohof A . Normal adult climbing fiber monoinnervation of cerebellar Purkinje cells in mice lacking MHC class I molecules. Dev Neurobiol. 2008; 68(8):997-1006. DOI: 10.1002/dneu.20639. View

14.

Oliveira A, Thams S, Lidman O, Piehl F, Hokfelt T, Karre K . A role for MHC class I molecules in synaptic plasticity and regeneration of neurons after axotomy. Proc Natl Acad Sci U S A. 2004; 101(51):17843-8. PMC: 539738. DOI: 10.1073/pnas.0408154101. View

15.

Tancredi V, Zona C, Velotti F, Eusebi F, Santoni A . Interleukin-2 suppresses established long-term potentiation and inhibits its induction in the rat hippocampus. Brain Res. 1990; 525(1):149-51. DOI: 10.1016/0006-8993(90)91331-a. View

16.

Jaaro-Peled H, Ayhan Y, Pletnikov M, Sawa A . Review of pathological hallmarks of schizophrenia: comparison of genetic models with patients and nongenetic models. Schizophr Bull. 2009; 36(2):301-13. PMC: 2833125. DOI: 10.1093/schbul/sbp133. View

17.

Kubota K, Inoue K, Hashimoto R, Kumamoto N, Kosuga A, Tatsumi M . Tumor necrosis factor receptor-associated protein 1 regulates cell adhesion and synaptic morphology via modulation of N-cadherin expression. J Neurochem. 2009; 110(2):496-508. DOI: 10.1111/j.1471-4159.2009.06099.x. View

18.

Chez M, Dowling T, Patel P, Khanna P, Kominsky M . Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatr Neurol. 2007; 36(6):361-5. DOI: 10.1016/j.pediatrneurol.2007.01.012. View

19.

Short S, Lubach G, Karasin A, Olsen C, Styner M, Knickmeyer R . Maternal influenza infection during pregnancy impacts postnatal brain development in the rhesus monkey. Biol Psychiatry. 2010; 67(10):965-73. PMC: 3235476. DOI: 10.1016/j.biopsych.2009.11.026. View

20.

Turrigiano G . The self-tuning neuron: synaptic scaling of excitatory synapses. Cell. 2008; 135(3):422-35. PMC: 2834419. DOI: 10.1016/j.cell.2008.10.008. View