Share This Article:

Region Specific Effects of Maternal Immune Activation on Offspring Neuroimmune Function

Abstract Full-Text HTML XML Download Download as PDF (Size:4857KB) PP. 51-63
DOI: 10.4236/oji.2015.52006    5,305 Downloads   5,742 Views   Citations
Author(s)    Leave a comment

ABSTRACT

Growing evidence suggests that maternal immune activation has a significant impact on the immuno-competence of the offspring. The present study aimed to characterize region-specific effects of maternal immune activation on the offspring’s neuroimmune function. The offspring born to dams treated with saline or lipopolysaccharide (LPS) at gestational day 18 was stimulated with saline or LPS at postnatal day 21, and the mRNA expression of various inflammatory genes in different brain regions of the offspring was analyzed. The offspring born to saline-treated dams exhibited a typical neuroimmune response with elevated levels of cytokines and chemokines following LPS stimulation in all four brain regions examined. In contrast, the offspring born to LPS- treated dams exhibited significantly reduced mRNA induction of cytokines and chemokines following LPS stimulation in the prefrontal cortex but not in the brainstem when compared with pups born to saline-treated dams. Furthermore, the mRNA expression of LPS-induced I-κBζ was significantly attenuated in the prefrontal cortex when compared with pups born to saline-treated dams. These results suggest that maternal LPS may have differential effects on the neuroimmune function in different regions of the offspring brain, and highlight the importance of maternal milieu in the development of neuroimmune function in the offspring.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

Zhou, H. (2015) Region Specific Effects of Maternal Immune Activation on Offspring Neuroimmune Function. Open Journal of Immunology, 5, 51-63. doi: 10.4236/oji.2015.52006.

References

[1] Hanke, M.L. and Kielian, T. (2011) Toll-Like Receptors in Health and Disease in the Brain: Mechanisms and Therapeutic Potential. Clinical Science (Lond), 121, 367-387.
http://dx.doi.org/10.1042/CS20110164
[2] Cutolo, M., Soldano, S., Contini, P., Sulli, A., Seriolo, B., Montagna, P. and Brizzolara, R. (2013) Intracellular NF- kB-Decrease and IKBalpha Increase in Human Macrophages Following CTLA4-Ig Treatment. Clinical and Experimental Rheumatology, 31, 943-946.
[3] Trinh, D.V., Zhu, N., Farhang, G., Kim, B.J. and Huxford, T. (2008) The Nuclear IkappaB Protein IkappaB Zeta Specifically Binds NF-kappaB p50 Homodimers and Forms a Ternary Complex on kappaB DNA. Journal of Molecular Biology, 379, 122-135.
http://dx.doi.org/10.1016/j.jmb.2008.03.060
[4] Kayama, H., Ramirez-Carrozzi, V.R., Yamamoto, M., Mizutani, T., Kuwata, H., Iba, H., Matsumoto, M., Honda, K., Smale, S.T. and Takeda, K. (2008) Class-Specific Regulation of Pro-Inflammatory Genes by MyD88 Pathways and IkappaBzeta. Journal of Biological Chemistry, 283, 12468-12477.
http://dx.doi.org/10.1074/jbc.M709965200
[5] Hildebrand, D.G., Alexander, E., Horber, S., Lehle, S., Obermayer, K., Munck, N.A., Rothfuss, O., Frick, J.S., Morimatsu, M., Schmitz, I., Roth, J., Ehrchen, J.M., Essmann, F. and Schulze-Osthoff, K. (2013) IkappaBzeta Is a Transcriptional Key Regulator of CCL2/MCP-1. Journal of Immunology, 190, 4812-4820.
[6] Huang, B., Yang, X.D., Lamb, A. and Chen, L.F. (2010) Posttranslational Modifications of NF-kappaB: Another Layer of Regulation for NF-kappaB Signaling Pathway. Cell Signal, 22, 1282-1290.
http://dx.doi.org/10.1016/j.cellsig.2010.03.017
[7] Zuckerman, L. and Weiner, I. (2005) Maternal Immune Activation Leads to Behavioral and Pharmacological Changes in the Adult Offspring. Journal of Psychiatric Research, 39, 311-323.
http://dx.doi.org/10.1016/j.jpsychires.2004.08.008
[8] Kramer, B.W., Ikegami, M., Moss, T.J., Nitsos, I., Newnham, J.P. and Jobe, A.H. (2005) Endotoxin-Induced Chorioamnionitis Modulates Innate Immunity of Monocytes in Preterm Sheep. American Journal of Respiratory and Critical Care Medicine, 171, 73-77.
http://dx.doi.org/10.1164/rccm.200406-745OC
[9] Hodyl, N.A., Krivanek, K.M., Lawrence, E., Clifton, V.L. and Hodgson, D.M. (2007) Prenatal Exposure to a Pro-In- flammatory Stimulus Causes Delays in the Development of the Innate Immune Response to LPS in the Offspring. Journal of Neuroimmunology, 190, 61-71.
http://dx.doi.org/10.1016/j.jneuroim.2007.07.021
[10] Lasala, N. and Zhou, H. (2007) Effects of Maternal Exposure to LPS on the Inflammatory Response in the Offspring. Journal of Neuroimmunology, 189, 95-101.
http://dx.doi.org/10.1016/j.jneuroim.2007.07.010
[11] Harnett, E.L., Dickinson, M.A. and Smith, G.N. (2007) Dose-Dependent Lipopolysaccharide-Induced Fetal Brain Injury in the Guinea Pig. American Journal of Obstetrics and Gynecology, 197, 179. e1-179. e7.
http://dx.doi.org/10.1016/j.ajog.2007.03.047
[12] Garay, P.A., Hsiao, E.Y., Patterson, P.H. and McAllister, A.K. (2013) Maternal Immune Activation Causes Age- and Region-Specific Changes in Brain cytokines in Offspring throughout Development. Brain, Behavior, and Immunity, 31, 54-68.
http://dx.doi.org/10.1016/j.bbi.2012.07.008
[13] Ortega, A., Jadeja, V. and Zhou, H.P. (2011) Postnatal Development of Lipopolysaccharide-induced Inflammatory Response in the Brain. Inflammation Research, 60, 175-185.
http://dx.doi.org/10.1007/s00011-010-0252-y
[14] Kitamura, H., Kanehira, K., Okita, K., Morimatsu, M. and Saito, M. (2000) MAIL, a Novel Nuclear IκB Protein That Potentiates LPS-Induced IL-6 Production. FEBS Letters, 485, 53-56.
http://dx.doi.org/10.1016/S0014-5793(00)02185-2
[15] Sun, S.C., Ganchi, P.A., Ballard, D.W. and Greene, W.C. (1993) NF-κB Controls Expression of Inhibitor IκB Alpha: Evidence for an Inducible Autoregulatory Pathway. Science, 259, 1912-1915.
http://dx.doi.org/10.1126/science.8096091
[16] Yamazaki, S., Muta, T., Matsuo, S. and Takeshige, K. (2005) Stimulus-Specific Induction of a Novel Nuclear Factor- κB Regulator, IκB-Zeta, via Toll/Interleukin-1 Receptor Is Mediated by mRNA Stabilization. Journal of Biological Chemistry, 280, 1678-1687.
http://dx.doi.org/10.1074/jbc.M409983200
[17] Kitamura, H., Kanehira, K., Shiina, T., Morimatsu, M., Jung, B.D., Akashi, S. and Saito, M. (2002) Bacterial Lipopolysaccharide Induces mRNA Expression of an IκB MAIL through Toll-Like Receptor 4. Journal of Veterinary Medical Science, 64, 419-422.
http://dx.doi.org/10.1292/jvms.64.419
[18] Ito, T., Morimatsu, M., Oonuma, T., Shiina, T., Kitamura, H. and Syuto, B. (2004) Transcriptional Regulation of the MAIL Gene in LPS-Stimulated RAW264 Mouse Macrophages. Gene, 342, 137-143.
http://dx.doi.org/10.1016/j.gene.2004.07.032
[19] Lehnardt, S. (2010) Innate Immunity and Neuroinflammation in the CNS: The Role of Microglia in Toll-Like Receptor-Mediated Neuronal Injury. Glia, 58, 253-263.
[20] Skaper, S.D. (2007) The Brain as a Target for Inflammatory Processes and Neuroprotective Strategies. Annals of the New York Academy of Sciences, 1122, 23-34.
http://dx.doi.org/10.1196/annals.1403.002
[21] Jean-Baptiste, E. (2007) Cellular Mechanisms in Sepsis. Journal of Intensive Care Medicine, 22, 63-72.
http://dx.doi.org/10.1177/0885066606297123
[22] Bosshart, H. and Heinzelmann, M. (2007) Targeting Bacterial Endotoxin: Two Sides of a Coin. Annals of the New York Academy of Sciences, 1096, 1-17.
http://dx.doi.org/10.1196/annals.1397.064
[23] Blasko, I., Stampfer-Kountchev, M., Robatscher, P., Veerhuis, R., Eikelenboom, P. and Grubeck-Loebenstein, B. (2004) How Chronic Inflammation Can Affect the Brain and Support the Development of Alzheimer’s Disease in Old Age: The Role of Microglia and Astrocytes. Aging Cell, 3, 169-176.
http://dx.doi.org/10.1111/j.1474-9728.2004.00101.x
[24] Sekiyama, K., Sugama, S., Fujita, M., Sekigawa, A., Takamatsu, Y., Waragai, M., Takenouchi, T. and Hashimoto, M. (2012) Neuroinflammation in Parkinson’s Disease and Related Disorders: A Lesson from Genetically Manipulated Mouse Models of Alpha-Synucleinopathies. Parkinson’s Disease, 2012, Article ID: 271732.
http://dx.doi.org/10.1155/2012/271732
[25] Napoli, I. and Neumann, H. (2009) Microglial Clearance Function in Health and Disease. Neuroscience, 158, 1030- 1038.
http://dx.doi.org/10.1016/j.neuroscience.2008.06.046
[26] Streit, W.J., Conde, J.R., Fendrick, S.E., Flanary, B.E. and Mariani, C.L. (2005) Role of Microglia in the Central Nervous System’s Immune Response. Neurological Research, 27, 685-691.
[27] Meyer, U. (2013) Developmental Neuroinflammation and Schizophrenia. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 42, 20-34.
http://dx.doi.org/10.1016/j.pnpbp.2011.11.003
[28] Zhou, H.P. (2012) Maternal Infection and Neurodevelopmental Disorders in the Offspring. American Journal of Immunology, 8, 10-17.
http://dx.doi.org/10.3844/ajisp.2012.10.17
[29] Boksa, P. (2008) Maternal Infection during Pregnancy and Schizophrenia. Journal of Psychiatry & Neuroscience, 33, 183-185.
[30] Buehler, M.R. (2011) A Proposed Mechanism for Autism: An Aberrant Neuroimmune Response Manifested as a Psychiatric Disorder. Medical Hypotheses, 76, 863-870.
http://dx.doi.org/10.1016/j.mehy.2011.02.038
[31] Graciarena, M., Depino, A.M. and Pitossi, F.J. (2010) Prenatal Inflammation Impairs Adult Neurogenesis and Memory Related Behavior through Persistent Hippocampal TGFβ1 Downregulation. Brain, Behavior, and Immunity, 24, 1301- 1309.
http://dx.doi.org/10.1016/j.bbi.2010.06.005

  
comments powered by Disqus

Copyright © 2018 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.