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17.1 Cells and Messengers of the Immune System

Alves de Lima, K., Rustenhoven, J., Da Mesquita, S., Wall, M., Salvador, A. F., Smirnov, I., Martelossi Cebinelli, G., Mamuladze, T., Baker, W., Papadopoulos, Z., Lopes, M. B., Cao, W. S., Xie, X. S., Herz, J., & Kipnis, J. (2020). Meningeal γδ T cells regulate anxiety-like behavior via IL-17a signaling in neurons. Nature Immunology, 21(11), 1421–1429. https://doi.org/10.1038/s41590-020-0776-4

Grob, B., Knapp, L. A., Martin, R. D., & Anzenberger, G. (1998). The major histocompatibility complex and mate choice: Inbreeding avoidance and selection of good genes. Experimental and Clinical Immunogenetics, 15(3), 119–129. https://doi.org/10.1159/000019063

Hanisch, U. K. (2002). Microglia as a source and target of cytokines. Glia, 40(2), 140–155. https://doi.org/10.1002/glia.10161

Havlicek, J., & Roberts, S. C. (2009). MHC-correlated mate choice in humans: A review. Psychoneuroendocrinology, 34(4), 497–512. https://doi.org/10.1016/j.psyneuen.2008.10.007

Havlíček, J., Winternitz, J., & Roberts, S. C. (2020). Major histocompatibility complex-associated odour preferences and human mate choice: Near and far horizons. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences, 375(1800), 20190260. https://doi.org/10.1098/rstb.2019.0260

Hopkins, S. J., & Rothwell, N. J. (1995). Cytokines and the nervous system. I: Expression and recognition. Trends in Neurosciences, 18(2), 83–88.

Iliff, J. J., Goldman, S. A., & Nedergaard, M. (2015). Implications of the discovery of brain lymphatic pathways. The Lancet. Neurology, 14(10), 977–979. https://doi.org/10.1016/S1474-4422(15)00221-5

Kipnis, J., Gadani, S., & Derecki, N. C. (2012). Pro-cognitive properties of T cells. Nature Reviews. Immunology, 12(9), 663–669. https://doi.org/10.1038/nri3280

Lord, G. (2002). Role of leptin in immunology. Nutrition Reviews, 60(10 Pt 2), S35–87. https://doi.org/10.1301/002966402320634913

Louveau, A., Smirnov, I., Keyes, T. J., Eccles, J. D., Rouhani, S. J., Peske, J. D., Derecki, N. C., Castle, D., Mandell, J. W., Lee, K. S., Harris, T. H., & Kipnis, J. (2015). Structural and functional features of central nervous system lymphatic vessels. Nature, 523(7560), 337–341. https://doi.org/10.1038/nature14432

Papayannopoulos, V. (2018). Neutrophil extracellular traps in immunity and disease. Nature Reviews. Immunology, 18(2), 134–147. https://doi.org/10.1038/nri.2017.105

Roth, O., Sundin, J., Berglund, A., Rosenqvist, G., & Wegner, K. M. (2014). Male mate choice relies on major histocompatibility complex class I in a sex-role-reversed pipefish. Journal of Evolutionary Biology, 27(5), 929–938. https://doi.org/10.1111/jeb.12365

Rothwell, N. J., & Hopkins, S. J. (1995). Cytokines and the nervous system II: Actions and mechanisms of action. Trends in Neurosciences, 18(3), 130–136. https://doi.org/10.1016/0166-2236(95)93890-a

Rymešová, D., Králová, T., Promerová, M., Bryja, J., Tomášek, O., Svobodová, J., Šmilauer, P., Šálek, M., & Albrecht, T. (2017). Mate choice for major histocompatibility complex complementarity in a strictly monogamous bird, the grey partridge (Perdix perdix). Frontiers in Zoology, 14, 9. https://doi.org/10.1186/s12983-017-0194-0

17.2 What Does Your Immune System Have to Do with Your Behavior?

Abazyan, B., Nomura, J., Kannan, G., Ishizuka, K., Tamashiro, K. L., Nucifora, F., Pogorelov, V., Ladenheim, B., Yang, C., Krasnova, I. N., Cadet, J. L., Pardo, C., Mori, S., Kamiya, A., Vogel, M. W., Sawa, A., Ross, C. A., & Pletnikov, M. V. (2010). Prenatal interaction of mutant DISC1 and immune activation produces adult psychopathology. Biological Psychiatry, 68(12), 1172–1181. https://doi.org/10.1016/j.biopsych.2010.09.022

Aubert, A., Goodall, G., Dantzer, R., & Gheusi, G. (1997). Differential effects of lipopolysaccharide on pup retrieving and nest building in lactating mice. Brain, Behavior, and Immunity, 11(2), 107–118. https://doi.org/10.1006/brbi.1997.0485

Avital, A., Goshen, I., Kamsler, A., Segal, M., Iverfeldt, K., Richter-Levin, G., & Yirmiya, R. (2003). Impaired interleukin-1 signaling is associated with deficits in hippocampal memory processes and neural plasticity. Hippocampus, 13(7), 826–834. https://doi.org/10.1002/hipo.10135

Blalock, J. E. (2005). The immune system as the sixth sense. Journal of Internal Medicine, 257(2), 126–138. https://doi.org/10.1111/j.1365-2796.2004.01441.x

Careaga, M., Van de Water, J., & Ashwood, P. (2010). Immune dysfunction in autism: A pathway to treatment. Neurotherapeutics: The Journal of the American Society for Experimental NeuroTherapeutics, 7(3), 283–292. https://doi.org/10.1016/j.nurt.2010.05.003

Carruthers, B. M., van de Sande, M. I., De Meirleir, K. L., Klimas, N. G., Broderick, G., Mitchell, T., Staines, D., Powles, A. C., Speight, N., Vallings, R., Bateman, L., Baumgarten-Austrheim, B., Bell, D. S., Carlo-Stella, N., Chia, J., Darragh, A., Jo, D., Lewis, D., Light, A. R., Marshall-Gradisnik, S., … Stevens, S. (2011). Myalgic encephalomyelitis: International Consensus Criteria. Journal of Internal Medicine, 270(4), 327–338. https://doi.org/10.1111/j.1365-2796.2011.02428.x

Devlin, B. A., Smith, C. J., & Bilbo, S. D. (2022). Sickness and the social brain: How the immune system regulates behavior across species. Brain, Behavior and Evolution, 97(3-4), 197–210. https://doi.org/10.1159/000521476

Garay, P. A., & McAllister, A. K. (2010). Novel roles for immune molecules in neural development: Implications for neurodevelopmental disorders. Frontiers in Synaptic Neuroscience, 2, 136. https://doi.org/10.3389/fnsyn.2010.00136

Harrison, N. A., Voon, V., Cercignani, M., Cooper, E. A., Pessiglione, M., & Critchley, H. D. (2016). A neurocomputational account of how inflammation enhances sensitivity to punishments versus rewards. Biological Psychiatry, 80(1), 73–81. https://doi.org/10.1016/j.biopsych.2015.07.018

Hart, B. L. (1988). Biological basis of the behavior of sick animals. Neuroscience and Biobehavioral Reviews, 12(2), 123–137. https://doi.org/10.1016/s0149-7634(88)80004-6

Kluger, M. J., Ringler, D. H., & Anver, M. R. (1975). Fever and survival. Science (New York, N.Y.), 188(4184), 166–168.

Miller, A. H., & Raison, C. L. (2016). The role of inflammation in depression: From evolutionary imperative to modern treatment target. Nature Reviews. Immunology, 16(1), 22–34. https://doi.org/10.1038/nri.2015.5

Müller, N., & Ackenheil, M. (1998). Psychoneuroimmunology and the cytokine action in the CNS: Implications for psychiatric disorders. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 22(1), 1–33. https://doi.org/10.1016/s0278-5846(97)00179-6

Muscatell, K. A., Moieni, M., Inagaki, T. K., Dutcher, J. M., Jevtic, I., Breen, E. C., Irwin, M. R., & Eisenberger, N. I. (2016). Exposure to an inflammatory challenge enhances neural sensitivity to negative and positive social feedback. Brain, Behavior, and Immunity, 57, 21–29. https://doi.org/10.1016/j.bbi.2016.03.022

Nemeth, D. P., & Quan, N. (2021). Modulation of neural networks by interleukin-1. Brain Plasticity (Amsterdam, Netherlands), 7(1), 17–32. https://doi.org/10.3233/BPL-200109

Quan, N., Whiteside, M., & Herkenham, M. (1998). Time course and localization patterns of interleukin-1beta messenger RNA expression in brain and pituitary after peripheral administration of lipopolysaccharide. Neuroscience, 83(1), 281–293. https://doi.org/10.1016/s0306-4522(97)00350-3

Vitkovic, L., Konsman, J. P., Bockaert, J., Dantzer, R., Homburger, V., & Jacque, C. (2000). Cytokine signals propagate through the brain. Molecular Psychiatry, 5(6), 604–615. https://doi.org/10.1038/sj.mp.4000813

Yirmiya, R., Avitsur, R., Donchin, O., & Cohen, E. (1995). Interleukin-1 inhibits sexual behavior in female but not in male rats. Brain, Behavior, and Immunity, 9(3), 220–233. https://doi.org/10.1006/brbi.1995.1021

17.3 How Does the Brain Talk to the Immune System?

Ader, R., Kelly, K., Moynihan, J. A., Grota, L. J., & Cohen, N. (1993). Conditioned enhancement of antibody production using antigen as the unconditioned stimulus. Brain, Behavior, and Immunity, 7(4), 334–343. https://doi.org/10.1006/brbi.1993.1033

Banks, W. A., & Erickson, M. A. (2010). The blood-brain barrier and immune function and dysfunction. Neurobiology of Disease, 37(1), 26–32. https://doi.org/10.1016/j.nbd.2009.07.031

Belcher, A. M., Ferré, S., Martinez, P. E., & Colloca, L. (2018). Role of placebo effects in pain and neuropsychiatric disorders. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 87(Pt B), 298–306. https://doi.org/10.1016/j.pnpbp.2017.06.003

Ben-Shaanan, T. L., Azulay-Debby, H., Dubovik, T., Starosvetsky, E., Korin, B., Schiller, M., Green, N. L., Admon, Y., Hakim, F., Shen-Orr, S. S., & Rolls, A. (2016). Activation of the reward system boosts innate and adaptive immunity. Nature Medicine, 22(8), 940–944. https://doi.org/10.1038/nm.4133

Ben-Shaanan, T. L., Schiller, M., Azulay-Debby, H., Korin, B., Boshnak, N., Koren, T., Krot, M., Shakya, J., Rahat, M. A., Hakim, F., & Rolls, A. (2018). Modulation of anti-tumor immunity by the brain's reward system. Nature Communications, 9(1), 2723. https://doi.org/10.1038/s41467-018-05283-5

Berkenbosch, F., van Oers, J., del Rey, A., Tilders, F., & Besedovsky, H. (1987). Corticotropin-releasing factor-producing neurons in the rat activated by interleukin-1. Science (New York, N.Y.), 238(4826), 524–526. https://doi.org/10.1126/science.2443979

Berthoud, H. R., & Neuhuber, W. L. (2000). Functional and chemical anatomy of the afferent vagal system. Autonomic Neuroscience: Basic & Clinical, 85(1-3), 1–17. https://doi.org/10.1016/S1566-0702(00)00215-0

Blatteis, C. M. (1992). Role of the OVLT in the febrile response to circulating pyrogens. Progress in Brain Research, 91, 409–412. https://doi.org/10.1016/s0079-6123(08)62360-2

Bordt, E. A., & Bilbo, S. D. (2020). Stressed-out T cells fragment the mind. Trends in Immunology, 41(2), 94–97. https://doi.org/10.1016/j.it.2019.12.008

Bosch, J. A., Engeland, C. G., Cacioppo, J. T., & Marucha, P. T. (2007). Depressive symptoms predict mucosal wound healing. Psychosomatic Medicine, 69(7), 597–605. https://doi.org/10.1097/PSY.0b013e318148c682

Caldwell, F. T., Graves, D. B., & Wallace, B. H. (1998). Studies on the mechanism of fever after intravenous administration of endotoxin. The Journal of Trauma, 44(2), 304–312. https://doi.org/10.1097/00005373-199802000-00012

Cohen, N., Moynihan, J. A., & Ader, R. (1994). Pavlovian conditioning of the immune system. International Archives of Allergy and Immunology, 105(2), 101–106. https://doi.org/10.1159/000236811

Dhabhar, F. S. (2000). Acute stress enhances while chronic stress suppresses skin immunity. The role of stress hormones and leukocyte trafficking. Annals of the New York Academy of Sciences, 917, 876–893. https://doi.org/10.1111/j.1749-6632.2000.tb05454.x

Dhabhar, F. S., & McEwen, B. S. (1999). Enhancing versus suppressive effects of stress hormones on skin immune function. Proceedings of the National Academy of Sciences of the United States of America, 96(3), 1059–1064. https://doi.org/10.1073/pnas.96.3.1059

Dhabhar, F. S., Miller, A. H., McEwen, B. S., & Spencer, R. L. (1996). Stress-induced changes in blood leukocyte distribution. Role of adrenal steroid hormones. Journal of Immunology (Baltimore, Md. : 1950), 157(4), 1638–1644.

Dhabhar, F. S., & Viswanathan, K. (2005). Short-term stress experienced at time of immunization induces a long-lasting increase in immunologic memory. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 289(3), R738–R744. https://doi.org/10.1152/ajpregu.00145.2005

Fan, K. Q., Li, Y. Y., Wang, H. L., Mao, X. T., Guo, J. X., Wang, F., Huang, L. J., Li, Y. N., Ma, X. Y., Gao, Z. J., Chen, W., Qian, D. D., Xue, W. J., Cao, Q., Zhang, L., Shen, L., Zhang, L., Tong, C., Zhong, J. Y., Lu, W., … Jin, J. (2019). Stress-induced metabolic disorder in peripheral CD4+ T cells leads to anxiety-like behavior. Cell, 179(4), 864–879.e19. https://doi.org/10.1016/j.cell.2019.10.001

Hallam, J., Jones, T., Alley, J., & Kohut, M. L. (2022). Exercise after influenza or COVID-19 vaccination increases serum antibody without an increase in side effects. Brain, Behavior, and Immunity, 102, 1–10. https://doi.org/10.1016/j.bbi.2022.02.005

Hansen, M. K., O'Connor, K. A., Goehler, L. E., Watkins, L. R., & Maier, S. F. (2001). The contribution of the vagus nerve in interleukin-1beta-induced fever is dependent on dose. American Journal of Physiology. Regulatory, Integrative and Comparative Physiology, 280(4), R929–R934. https://doi.org/10.1152/ajpregu.2001.280.4.R929

Hawkins, B. T., & Davis, T. P. (2005). The blood-brain barrier/neurovascular unit in health and disease. Pharmacological Reviews, 57(2), 173–185. https://doi.org/10.1124/pr.57.2.4

Irwin, M., Patterson, T., Smith, T. L., Caldwell, C., Brown, S. A., Gillin, J. C., & Grant, I. (1990). Reduction of immune function in life stress and depression. Biological Psychiatry, 27(1), 22–30. https://doi.org/10.1016/0006-3223(90)90016-u

Kiecolt-Glaser, J. K., Marucha, P. T., Malarkey, W. B., Mercado, A. M., & Glaser, R. (1995). Slowing of wound healing by psychological stress. Lancet (London, England), 346(8984), 1194–1196. https://doi.org/10.1016/s0140-6736(95)92899-5

Lee, H. Y., Whiteside, M. B., & Herkenham, M. (1998). Area postrema removal abolishes stimulatory effects of intravenous interleukin-1beta on hypothalamic-pituitary-adrenal axis activity and c-fos mRNA in the hypothalamic paraventricular nucleus. Brain Research Bulletin, 46(6), 495–503. https://doi.org/10.1016/s0361-9230(98)00045-8

Luheshi, G. N., Bluthé, R. M., Rushforth, D., Mulcahy, N., Konsman, J. P., Goldbach, M., & Dantzer, R. (2000). Vagotomy attenuates the behavioural but not the pyrogenic effects of interleukin-1 in rats. Autonomic Neuroscience: Basic & Clinical, 85(1-3), 127–132. https://doi.org/10.1016/S1566-0702(00)00231-9

Maier, S. F., & Watkins, L. R. (1998). Cytokines for psychologists: Implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychological Review, 105(1), 83–107. https://doi.org/10.1037/0033-295x.105.1.83

Marucha, P. T., Kiecolt-Glaser, J. K., & Favagehi, M. (1998). Mucosal wound healing is impaired by examination stress. Psychosomatic Medicine, 60(3), 362–365. https://doi.org/10.1097/00006842-199805000-00025

McKim, D. B., Weber, M. D., Niraula, A., Sawicki, C. M., Liu, X., Jarrett, B. L., Ramirez-Chan, K., Wang, Y., Roeth, R. M., Sucaldito, A. D., Sobol, C. G., Quan, N., Sheridan, J. F., & Godbout, J. P. (2018). Microglial recruitment of IL-1β-producing monocytes to brain endothelium causes stress-induced anxiety. Molecular Psychiatry, 23(6), 1421–1431. https://doi.org/10.1038/mp.2017.64

Medawar, P. B. (1948). Immunity to homologous grafted skin; the fate of skin homografts transplanted to the brain, to subcutaneous tissue, and to the anterior chamber of the eye. British Journal of Experimental Pathology, 29(1), 58–69.

Pan, W., & Kastin, A. J. (2008). Cytokine transport across the injured blood-spinal cord barrier. Current Pharmaceutical Design, 14(16), 1620–1624. https://doi.org/10.2174/138161208784705450

Rosas-Ballina, M., Olofsson, P. S., Ochani, M., Valdés-Ferrer, S. I., Levine, Y. A., Reardon, C., Tusche, M. W., Pavlov, V. A., Andersson, U., Chavan, S., Mak, T. W., & Tracey, K. J. (2011). Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science (New York, N.Y.), 334(6052), 98–101. https://doi.org/10.1126/science.1209985

Rosenberger, P. H., Jokl, P., & Ickovics, J. (2006). Psychosocial factors and surgical outcomes: An evidence-based literature review. The Journal of the American Academy of Orthopaedic Surgeons, 14(7), 397–405. https://doi.org/10.5435/00124635-200607000-00002

Sainz, B., Loutsch, J. M., Marquart, M. E., & Hill, J. M. (2001). Stress-associated immunomodulation and herpes simplex virus infections. Medical Hypotheses, 56(3), 348–356. https://doi.org/10.1054/mehy.2000.1219

Sapolsky, R., Rivier, C., Yamamoto, G., Plotsky, P., & Vale, W. (1987). Interleukin-1 stimulates the secretion of hypothalamic corticotropin-releasing factor. Science (New York, N.Y.), 238(4826), 522–524. https://doi.org/10.1126/science.2821621

Sapolsky, R. M., Romero, L. M., & Munck, A. U. (2000). How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocrine Reviews, 21(1), 55–89. https://doi.org/10.1210/edrv.21.1.0389

Tracey, K. J. (2002). The inflammatory reflex. Nature, 420(6917), 853–859. https://doi.org/10.1038/nature01321

Turnbull, A. V., & Rivier, C. L. (1999). Regulation of the hypothalamic-pituitary-adrenal axis by cytokines: Actions and mechanisms of action. Physiological Reviews, 79(1), 1–71. https://doi.org/10.1152/physrev.1999.79.1.1

Weber, M. D., Godbout, J. P., & Sheridan, J. F. (2017). Repeated social defeat, neuroinflammation, and behavior: Monocytes carry the signal. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 42(1), 46–61. https://doi.org/10.1038/npp.2016.102

Wexler, B. C., Dolgin, A. E., & Tryczynski, E. W. (1957). Effects of a bacterial polysaccharide (piromen) on the pituitary-adrenal axis: Adrenal ascorbic acid, cholesterol and histologic alterations. Endocrinology, 61(3), 300–308. https://doi.org/10.1210/endo-61-3-300

Yarlagadda, A., Alfson, E., & Clayton, A. H. (2009). The blood brain barrier and the role of cytokines in neuropsychiatry. Psychiatry (Edgmont (Pa. : Township)), 6(11), 18–22.

17.4 What Do Immune System Signals Do Once They Reach the Brain?

Atladóttir, H. O., Thorsen, P., Østergaard, L., Schendel, D. E., Lemcke, S., Abdallah, M., & Parner, E. T. (2010). Maternal infection requiring hospitalization during pregnancy and autism spectrum disorders. Journal of Autism and Developmental Disorders, 40(12), 1423–1430. https://doi.org/10.1007/s10803-010-1006-y

Ayata, P., Badimon, A., Strasburger, H. J., Duff, M. K., Montgomery, S. E., Loh, Y. E., Ebert, A., Pimenova, A. A., Ramirez, B. R., Chan, A. T., Sullivan, J. M., Purushothaman, I., Scarpa, J. R., Goate, A. M., Busslinger, M., Shen, L., Losic, B., & Schaefer, A. (2018). Epigenetic regulation of brain region-specific microglia clearance activity. Nature Neuroscience, 21(8), 1049–1060. https://doi.org/10.1038/s41593-018-0192-3

Bessis, A., Béchade, C., Bernard, D., & Roumier, A. (2007). Microglial control of neuronal death and synaptic properties. Glia, 55(3), 233–238. https://doi.org/10.1002/glia.20459

Bilbo, S. D., Block, C. L., Bolton, J. L., Hanamsagar, R., & Tran, P. K. (2018). Beyond infection - Maternal immune activation by environmental factors, microglial development, and relevance for autism spectrum disorders. Experimental Neurology, 299(Pt A), 241–251. https://doi.org/10.1016/j.expneurol.2017.07.002

Block, C. L., Eroglu, O., Mague, S. D., Smith, C. J., Ceasrine, A. M., Sriworarat, C., Blount, C., Beben, K. A., Malacon, K. E., Ndubuizu, N., Talbot, A., Gallagher, N. M., Chan Jo, Y., Nyangacha, T., Carlson, D. E., Dzirasa, K., Eroglu, C., & Bilbo, S. D. (2022). Prenatal environmental stressors impair postnatal microglia function and adult behavior in males. Cell Reports, 40(5), 111161. https://doi.org/10.1016/j.celrep.2022.111161

Cao, P., Chen, C., Liu, A., Shan, Q., Zhu, X., Jia, C., Peng, X., Zhang, M., Farzinpour, Z., Zhou, W., Wang, H., Zhou, J. N., Song, X., Wang, L., Tao, W., Zheng, C., Zhang, Y., Ding, Y. Q., Jin, Y., Xu, L., & Zhang, Z. (2021). Early-life inflammation promotes depressive symptoms in adolescence via microglial engulfment of dendritic spines. Neuron, 109(16), 2573–2589.e9. https://doi.org/10.1016/j.neuron.2021.06.012

Chambers, R. A., Taylor, J. R., & Potenza, M. N. (2003). Developmental neurocircuitry of motivation in adolescence: A critical period of addiction vulnerability. The American Journal of Psychiatry, 160(6), 1041–1052. https://doi.org/10.1176/appi.ajp.160.6.1041

Chen, S. K., Tvrdik, P., Peden, E., Cho, S., Wu, S., Spangrude, G., & Capecchi, M. R. (2010). Hematopoietic origin of pathological grooming in Hoxb8 mutant mice. Cell, 141(5), 775–785. https://doi.org/10.1016/j.cell.2010.03.055

Cooper, S. J. (2005). Donald O. Hebb's synapse and learning rule: A history and commentary. Neuroscience and Biobehavioral Reviews, 28(8), 851–874. https://doi.org/10.1016/j.neubiorev.2004.09.009

Cotella, E. M., Gómez, A. S., Lemen, P., Chen, C., Fernández, G., Hansen, C., Herman, J. P., & Paglini, M. G. (2019). Long-term impact of chronic variable stress in adolescence versus adulthood. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 88, 303–310. https://doi.org/10.1016/j.pnpbp.2018.08.003

Cunningham, C. L., Martínez-Cerdeño, V., & Noctor, S. C. (2013). Microglia regulate the number of neural precursor cells in the developing cerebral cortex. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 33(10), 4216–4233. https://doi.org/10.1523/JNEUROSCI.3441-12.2013

Davalos, D., Grutzendler, J., Yang, G., Kim, J. V., Zuo, Y., Jung, S., Littman, D. R., Dustin, M. L., & Gan, W. B. (2005). ATP mediates rapid microglial response to local brain injury in vivo. Nature Neuroscience, 8(6), 752–758. https://doi.org/10.1038/nn1472

De, S., Van Deren, D., Peden, E., Hockin, M., Boulet, A., Titen, S., & Capecchi, M. R. (2018). Two distinct ontogenies confer heterogeneity to mouse brain microglia. Development (Cambridge, England), 145(13), dev152306. https://doi.org/10.1242/dev.152306

Dziabis, J. E., & Bilbo, S. D. (2022). Microglia and sensitive periods in brain development. Current Topics in Behavioral Neurosciences, 53, 55–78. https://doi.org/10.1007/7854_2021_242

Giovanoli, S., Engler, H., Engler, A., Richetto, J., Feldon, J., Riva, M. A., Schedlowski, M., & Meyer, U. (2016). Preventive effects of minocycline in a neurodevelopmental two-hit model with relevance to schizophrenia. Translational Psychiatry, 6(4), e772. https://doi.org/10.1038/tp.2016.38

Hume, D. A., Caruso, M., Ferrari-Cestari, M., Summers, K. M., Pridans, C., & Irvine, K. M. (2020). Phenotypic impacts of CSF1R deficiencies in humans and model organisms. Journal of Leukocyte Biology, 107(2), 205–219. https://doi.org/10.1002/JLB.MR0519-143R

Hanamsagar, R., & Bilbo, S. D. (2017). Environment matters: Microglia function and dysfunction in a changing world. Current Opinion in Neurobiology, 47, 146–155. https://doi.org/10.1016/j.conb.2017.10.007

Hong, S., Beja-Glasser, V. F., Nfonoyim, B. M., Frouin, A., Li, S., Ramakrishnan, S., Merry, K. M., Shi, Q., Rosenthal, A., Barres, B. A., Lemere, C. A., Selkoe, D. J., & Stevens, B. (2016). Complement and microglia mediate early synapse loss in Alzheimer mouse models. Science (New York, N.Y.), 352(6286), 712–716. https://doi.org/10.1126/science.aad8373

Knuesel, I., Chicha, L., Britschgi, M., Schobel, S. A., Bodmer, M., Hellings, J. A., Toovey, S., & Prinssen, E. P. (2014). Maternal immune activation and abnormal brain development across CNS disorders. Nature Reviews. Neurology, 10(11), 643–660. https://doi.org/10.1038/nrneurol.2014.187

Kopec, A. M., Smith, C. J., Ayre, N. R., Sweat, S. C., & Bilbo, S. D. (2018). Microglial dopamine receptor elimination defines sex-specific nucleus accumbens development and social behavior in adolescent rats. Nature Communications, 9(1), 3769. https://doi.org/10.1038/s41467-018-06118-z

Kopec, A. M., Smith, C. J., & Bilbo, S. D. (2019). Neuro-immune mechanisms regulating social behavior: Dopamine as mediator?. Trends in Neurosciences, 42(5), 337–348. https://doi.org/10.1016/j.tins.2019.02.005

Kwon, H. K., Choi, G. B., & Huh, J. R. (2022). Maternal inflammation and its ramifications on fetal neurodevelopment. Trends in Immunology, 43(3), 230–244. https://doi.org/10.1016/j.it.2022.01.007

Li, Y., Du, X. F., Liu, C. S., Wen, Z. L., & Du, J. L. (2012). Reciprocal regulation between resting microglial dynamics and neuronal activity in vivo. Developmental Cell, 23(6), 1189–1202. https://doi.org/10.1016/j.devcel.2012.10.027

Luo, L., & O'Leary, D. D. (2005). Axon retraction and degeneration in development and disease. Annual Review of Neuroscience, 28, 127–156. https://doi.org/10.1146/annurev.neuro.28.061604.135632

Lynch, M. A. (2022). Exploring sex-related differences in microglia may be a game-changer in precision medicine. Frontiers in Aging Neuroscience, 14, 868448. https://doi.org/10.3389/fnagi.2022.868448

Marín-Teva, J. L., Dusart, I., Colin, C., Gervais, A., van Rooijen, N., & Mallat, M. (2004). Microglia promote the death of developing Purkinje cells. Neuron, 41(4), 535–547. https://doi.org/10.1016/s0896-6273(04)00069-8

Nguyen, P. T., Dorman, L. C., Pan, S., Vainchtein, I. D., Han, R. T., Nakao-Inoue, H., Taloma, S. E., Barron, J. J., Molofsky, A. B., Kheirbek, M. A., & Molofsky, A. V. (2020). Microglial remodeling of the extracellular matrix promotes synapse plasticity. Cell, 182(2), 388–403.e15. https://doi.org/10.1016/j.cell.2020.05.050

Nimmerjahn, A., Kirchhoff, F., & Helmchen, F. (2005). Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science (New York, N.Y.), 308(5726), 1314–1318. https://doi.org/10.1126/science.1110647

Oosterhof, N., Chang, I. J., Karimiani, E. G., Kuil, L. E., Jensen, D. M., Daza, R., Young, E., Astle, L., van der Linde, H. C., Shivaram, G. M., Demmers, J., Latimer, C. S., Keene, C. D., Loter, E., Maroofian, R., van Ham, T. J., Hevner, R. F., & Bennett, J. T. (2019). Homozygous mutations in CSF1R cause a pediatric-onset leukoencephalopathy and can result in congenital absence of microglia. American Journal of Human Genetics, 104(5), 936–947. https://doi.org/10.1016/j.ajhg.2019.03.010

Schafer, D. P., Lehrman, E. K., Kautzman, A. G., Koyama, R., Mardinly, A. R., Yamasaki, R., Ransohoff, R. M., Greenberg, M. E., Barres, B. A., & Stevens, B. (2012). Microglia sculpt postnatal neural circuits in an activity and complement-dependent manner. Neuron, 74(4), 691–705. https://doi.org/10.1016/j.neuron.2012.03.026

Sekar, A., Bialas, A. R., de Rivera, H., Davis, A., Hammond, T. R., Kamitaki, N., Tooley, K., Presumey, J., Baum, M., Van Doren, V., Genovese, G., Rose, S. A., Handsaker, R. E., Schizophrenia Working Group of the Psychiatric Genomics Consortium, Daly, M. J., Carroll, M. C., Stevens, B., & McCarroll, S. A. (2022). Author correction: Schizophrenia risk from complex variation of complement component 4. Nature, 601(7892), E4–E5. https://doi.org/10.1038/s41586-021-04202-x

Smith, S. E., Li, J., Garbett, K., Mirnics, K., & Patterson, P. H. (2007). Maternal immune activation alters fetal brain development through interleukin-6. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 27(40), 10695–10702. https://doi.org/10.1523/JNEUROSCI.2178-07.2007

Wake, H., Moorhouse, A. J., Jinno, S., Kohsaka, S., & Nabekura, J. (2009). Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 29(13), 3974–3980. https://doi.org/10.1523/JNEUROSCI.4363-08.2009

Wang, C., Yue, H., Hu, Z., Shen, Y., Ma, J., Li, J., Wang, X. D., Wang, L., Sun, B., Shi, P., Wang, L., & Gu, Y. (2020). Microglia mediate forgetting via complement-dependent synaptic elimination. Science (New York, N.Y.), 367(6478), 688–694. https://doi.org/10.1126/science.aaz2288

Werneburg, S., Jung, J., Kunjamma, R. B., Ha, S. K., Luciano, N. J., Willis, C. M., Gao, G., Biscola, N. P., Havton, L. A., Crocker, S. J., Popko, B., Reich, D. S., & Schafer, D. P. (2020). Targeted complement inhibition at synapses prevents microglial synaptic engulfment and synapse loss in demyelinating disease. Immunity, 52(1), 167–182.e7. https://doi.org/10.1016/j.immuni.2019.12.004

Williamson, L. L., Sholar, P. W., Mistry, R. S., Smith, S. H., & Bilbo, S. D. (2011). Microglia and memory: Modulation by early-life infection. The Journal of Neuroscience: The Official Journal of the Society for Neuroscience, 31(43), 15511–15521. https://doi.org/10.1523/JNEUROSCI.3688-11.2011

Yohn, N. L., & Blendy, J. A. (2017). Adolescent chronic unpredictable stress exposure is a sensitive window for long-term changes in adult behavior in mice. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 42(8), 1670–1678. https://doi.org/10.1038/npp.2017.11

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