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Prenatal Alcohol Exposure: Impact on Neuroendocrine–Neuroimmune Networks

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Neural-Immune Interactions in Brain Function and Alcohol Related Disorders

Abstract

Alcohol exposure in utero can have numerous adverse effects on a developing fetus. The term fetal alcohol spectrum disorder (FASD) refers to the broad spectrum of structural, neurocognitive, and behavioral abnormalities or deficits that can occur following prenatal alcohol (ethanol) exposure (PAE). At the most severe end of the spectrum is fetal alcohol syndrome (FAS), which involves the complete phenotype of characteristic facial anomalies, growth retardation, and central nervous system (CNS) abnormalities. Alcohol exposure at levels that result in some but not all components of the facial, growth, and CNS deficits, and with evidence of neurobehavioral abnormalities, is termed partial fetal alcohol syndrome (PFAS). In the absence of any facial anomalies or growth deficits, a range of effects can occur that may be primarily physical, termed alcohol-related birth defects (ARBD), or primarily neurological and/or neurobehavioral, termed alcohol-related neurodevelopmental disorder (ARND) [1].

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References

  1. Stratton K, Howe C, Battaglia F (1996) Fetal alcohol syndrome; diagnosis, epidemiology, prevention and treatment. National Academy Press, Washington

    Google Scholar 

  2. Holsapple MP, West LJ, Landreth KS (2003) Species comparison of anatomical and functional immune system development. Birth Defects Res B Dev Reprod Toxicol 68:321–334

    Article  PubMed  CAS  Google Scholar 

  3. Bilbo SD, Schwarz JM (2009) Early-life programming of later-life brain and behavior: a critical role for the immune system. Front Behav Neurosci 3:14

    Article  PubMed  CAS  Google Scholar 

  4. Gill TJ 3rd et al (1983) Transplacental immunization of the human fetus to tetanus by immunization of the mother. J Clin Invest 72:987–996

    Article  PubMed  Google Scholar 

  5. King CL et al (1998) B cell sensitization to helminthic infection develops in utero in humans. J Immunol 160:3578–3584

    PubMed  CAS  Google Scholar 

  6. Migliaccio G et al (1986) Human embryonic hemopoiesis. Kinetics of progenitors and precursors underlying the yolk sac—liver transition. J Clin Invest 78:51–60

    Article  PubMed  CAS  Google Scholar 

  7. Holt PG, Jones CA (2000) The development of the immune system during pregnancy and early life. Allergy 55:688–697

    Article  PubMed  CAS  Google Scholar 

  8. Goldblatt D (1998) Immunisation and the maturation of infant immune responses. Dev Biol Stand 95:125–132

    PubMed  CAS  Google Scholar 

  9. Peakman M, Buggins AG, Nicolaides KH, Layton DM, Vergani D (1992) Analysis of lymphocyte phenotypes in cord blood from early gestation fetuses. Clin Exp Immunol 90:345–350

    Article  PubMed  CAS  Google Scholar 

  10. West LJ (2002) Defining critical windows in the development of the human immune system. Hum Exp Toxicol 21:499–505

    Article  PubMed  CAS  Google Scholar 

  11. Kay HE, Doe J, Hockley A (1970) Response of human foetal thymocytes to phytohaemagglutinin (PHA). Immunology 18:393–396

    PubMed  CAS  Google Scholar 

  12. Hofman FM, Danilovs J, Husmann L, Taylor CR (1984) Ontogeny of B cell markers in the human fetal liver. J Immunol 133:1197–1201

    PubMed  CAS  Google Scholar 

  13. Bockman DE (1997) Development of the thymus. Microsc Res Tech 38:209–215

    Article  PubMed  CAS  Google Scholar 

  14. Berry SM et al (1992) Circulating lymphocyte subsets in second- and third-trimester fetuses: comparison with newborns and adults. Am J Obstet Gynecol 167:895–900

    PubMed  CAS  Google Scholar 

  15. Zajac CS, Abel EL (1992) Animal models of prenatal alcohol exposure. Int J Epidemiol 21(Suppl 1):S24–S32

    PubMed  Google Scholar 

  16. Johnson S, Knight R, Marmer DJ, Steele RW (1981) Immune deficiency in fetal alcohol syndrome. Pediatr Res 15:908–911

    Article  PubMed  CAS  Google Scholar 

  17. Church MW, Kaltenbach JA (1997) Hearing, speech, language, and vestibular disorders in the fetal alcohol syndrome: a literature review. Alcohol Clin Exp Res 21:495–512

    PubMed  CAS  Google Scholar 

  18. Ammann AJ, Wara DW, Cowan MJ, Barrett DJ, Stiehm ER (1982) The DiGeorge syndrome and the fetal alcohol syndrome. Am J Dis Child 136:906–908

    PubMed  CAS  Google Scholar 

  19. Oleson DR, Magee RM, Donahoe RM, Falek A, Coles CD (1998) Immunity and prenatal alcohol exposure. A pilot study in human adolescents. Adv Exp Med Biol 437:255–264

    Article  PubMed  CAS  Google Scholar 

  20. Gauthier TW, Manar MH, Brown LA (2004) Is maternal alcohol use a risk factor for early-onset sepsis in premature newborns? Alcohol 33:139–145

    PubMed  CAS  Google Scholar 

  21. Lemons JA et al (2001) Very low birth weight outcomes of the National Institute of Child Health and Human Development Neonatal Research Network, January 1995 through December 1996. NICHD Neonatal Research Network. Pediatrics 107:E1

    Article  PubMed  CAS  Google Scholar 

  22. Jerrells TR, Eckardt MJ, Weinberg J (1990) Mechanisms of ethanol-induced immunosuppression. Prog Clin Biol Res 325:173–180

    PubMed  CAS  Google Scholar 

  23. Gauthier TW, Drews-Botsch C, Falek A, Coles C, Brown LA (2005) Maternal alcohol abuse and neonatal infection. Alcohol Clin Exp Res 29:1035–1043

    Article  PubMed  Google Scholar 

  24. Abel EL, Hannigan JH (1995) Maternal risk factors in fetal alcohol syndrome: provocative and permissive influences. Neurotoxicol Teratol 17:445–462

    Article  PubMed  CAS  Google Scholar 

  25. Dietert RR, Piepenbrink MS (2008) The managed immune system: protecting the womb to delay the tomb. Hum Exp Toxicol 27:129–134

    Article  PubMed  Google Scholar 

  26. Suckow MA, Weisbroth SH, Franklin CL, NetLibrary Inc. (2006) The laboratory rat. In: American College of Laboratory Animal Medicine series xvi. Elsevier, Amsterdam, 912 p

    Google Scholar 

  27. Hendrickx AG, Makori N, Peterson P (2000) Nonhuman primates: their role in assessing developmental effects of immunomodulatory agents. Hum Exp Toxicol 19:219–225

    Article  PubMed  CAS  Google Scholar 

  28. Hendrickx AG, Makori N, Peterson P (2002) The nonhuman primate as a model of developmental immunotoxicity. Hum Exp Toxicol 21:537–542

    Article  PubMed  CAS  Google Scholar 

  29. Neubert RT, Webb JR, Neubert D (2002) Feasibility of human trials to assess developmental immunotoxicity, and some comparison with data on New World monkeys. Hum Exp Toxicol 21:543–567

    Article  PubMed  CAS  Google Scholar 

  30. Barreiro LB, Marioni JC, Blekhman R, Stephens M, Gilad Y (2010) Functional comparison of innate immune signaling pathways in primates. PLoS Genet 6:e1001249

    Article  PubMed  CAS  Google Scholar 

  31. Zhang X, Sliwowska JH, Weinberg J (2005) Prenatal alcohol exposure and fetal programming: effects on neuroendocrine and immune function. Exp Biol Med (Maywood) 230:376–388

    CAS  Google Scholar 

  32. Weinberg J (1994) Recent studies on the effects of fetal alcohol exposure on the endocrine and immune systems. Alcohol Alcohol Suppl 2:401–409

    PubMed  CAS  Google Scholar 

  33. Grossmann A et al (1993) Immune function in offspring of nonhuman primates (Macaca nemestrina) exposed weekly to 1.8 g/kg ethanol during pregnancy: preliminary observations. Alcohol Clin Exp Res 17:822–827

    Article  PubMed  CAS  Google Scholar 

  34. Ewald SJ, Walden SM (1988) Flow cytometric and histological analysis of mouse thymus in fetal alcohol syndrome. J Leukoc Biol 44:434–440

    PubMed  CAS  Google Scholar 

  35. Ewald SJ, Frost WW (1987) Effect of prenatal exposure to ethanol on development of the thymus. Thymus 9:211–215

    PubMed  CAS  Google Scholar 

  36. Redei E, Clark WR, McGivern RF (1989) Alcohol exposure in utero results in diminished T-cell function and alterations in brain corticotropin-releasing factor and ACTH content. Alcohol Clin Exp Res 13:439–443

    Article  PubMed  CAS  Google Scholar 

  37. Ewald SJ (1989) T lymphocyte populations in fetal alcohol syndrome. Alcohol Clin Exp Res 13:485–489

    Article  PubMed  CAS  Google Scholar 

  38. Giberson PK, Blakley BR (1994) Effect of postnatal ethanol exposure on expression of differentiation antigens of murine splenic lymphocytes. Alcohol Clin Exp Res 18:21–28

    Article  PubMed  CAS  Google Scholar 

  39. Taylor AN, Tio DL, Chiappelli F (1999) Thymocyte development in male fetal alcohol-exposed rats. Alcohol Clin Exp Res 23:465–470

    Article  PubMed  CAS  Google Scholar 

  40. Chiappelli F, Tio D, Tritt SH, Pilati ML, Taylor AN (1992) Selective effects of fetal alcohol exposure on rat thymocyte development. Alcohol 9:481–487

    Article  PubMed  CAS  Google Scholar 

  41. Wong CM et al (1992) Prenatal exposure to alcohol enhances thymocyte mitogenic responses postnatally. Int J Immunopharmacol 14:303–309

    Article  PubMed  CAS  Google Scholar 

  42. Bray LA, Shao H, Ewald SJ (1993) Effect of ethanol on development of fetal mouse thymocytes in organ culture. Cell Immunol 151:12–23

    Article  PubMed  Google Scholar 

  43. Ewald SJ, Huang C, Bray L (1991) Effect of prenatal alcohol exposure on lymphocyte populations in mice. Adv Exp Med Biol 288:237–244

    Article  PubMed  CAS  Google Scholar 

  44. Ewald SJ, Shao H (1993) Ethanol increases apoptotic cell death of thymocytes in vitro. Alcohol Clin Exp Res 17:359–365

    Article  PubMed  CAS  Google Scholar 

  45. Ewald SJ, Huang C (1990) Lymphocyte populations and immune responses in mice prenatally exposed to ethanol. Prog Clin Biol Res 325:191–200

    PubMed  CAS  Google Scholar 

  46. Giberson PK et al (1997) The effect of cold stress on lymphocyte proliferation in fetal ethanol-exposed rats. Alcohol Clin Exp Res 21:1440–1447

    Article  PubMed  CAS  Google Scholar 

  47. Monjan AA, Mandell W (1980) Fetal alcohol and immunity: depression of mitogen-induced lymphocyte blastogenesis. Neurobehav Toxicol 2:213–215

    CAS  Google Scholar 

  48. Norman DC, Chang MP, Castle SC, Van Zuylen JE, Taylor AN (1989) Diminished proliferative response of con A-blast cells to interleukin 2 in adult rats exposed to ethanol in utero. Alcohol Clin Exp Res 13:69–72

    Article  PubMed  CAS  Google Scholar 

  49. Weinberg J, Jerrells TR (1991) Suppression of immune responsiveness: sex differences in prenatal ethanol effects. Alcohol Clin Exp Res 15:525–531

    Article  PubMed  CAS  Google Scholar 

  50. Grossman CJ et al (1993) Sex differences and the effects of alcohol on immune response in male and female rats. Alcohol Clin Exp Res 17:832–840

    Article  PubMed  CAS  Google Scholar 

  51. Gottesfeld Z, Ullrich SE (1995) Prenatal alcohol exposure selectively suppresses cell-mediated but not humoral immune responsiveness. Int J Immunopharmacol 17:247–254

    Article  PubMed  CAS  Google Scholar 

  52. Jerrells TR, Weinberg J (1998) Influence of ethanol consumption on immune competence of adult animals exposed to ethanol in utero. Alcohol Clin Exp Res 22:391–400

    Article  PubMed  CAS  Google Scholar 

  53. Gottesfeld Z, Abel EL (1991) Maternal and paternal alcohol use: effects on the immune system of the offspring. Life Sci 48:1–8

    Article  PubMed  CAS  Google Scholar 

  54. Norman DC et al (1991) Changes with age in the proliferative response of splenic T cells from rats exposed to ethanol in utero. Alcohol Clin Exp Res 15:428–432

    Article  PubMed  CAS  Google Scholar 

  55. Gottesfeld Z, Christie R, Felten DL, LeGrue SJ (1990) Prenatal ethanol exposure alters immune capacity and noradrenergic synaptic transmission in lymphoid organs of the adult mouse. Neuroscience 35:185–194

    Article  PubMed  CAS  Google Scholar 

  56. McGill J et al (2009) Fetal exposure to ethanol has long-term effects on the severity of influenza virus infections. J Immunol 182:7803–7808

    Article  PubMed  CAS  Google Scholar 

  57. Wolcott RM, Jennings SR, Chervenak R (1995) In utero exposure to ethanol affects postnatal development of T- and B-lymphocytes, but not natural killer cells. Alcohol Clin Exp Res 19:170–176

    Article  PubMed  CAS  Google Scholar 

  58. Biber KL, Moscatello KM, Dempsey DC, Chervenak R, Wolcott RM (1998) Effects of in utero alcohol exposure on B-cell development in the murine fetal liver. Alcohol Clin Exp Res 22:1706–1712

    Article  PubMed  CAS  Google Scholar 

  59. Moscatello KM, Biber KL, Jennings SR, Chervenak R, Wolcott RM (1999) Effects of in utero alcohol exposure on B cell development in neonatal spleen and bone marrow. Cell Immunol 191:124–130

    Article  PubMed  CAS  Google Scholar 

  60. Robinson RS, Seelig LL Jr (2002) Effects of maternal ethanol consumption on hematopoietic cells in the rat fetal liver. Alcohol 28:151–156

    Article  PubMed  CAS  Google Scholar 

  61. Clarren SK, Bowden DM (1982) Fetal alcohol syndrome: a new primate model for binge drinking and its relevance to human ethanol teratogenesis. J Pediatr 101:819–824

    Article  PubMed  CAS  Google Scholar 

  62. Clarren SK, Astley SJ, Bowden DM (1988) Physical anomalies and developmental delays in nonhuman primate infants exposed to weekly doses of ethanol during gestation. Teratology 37:561–569

    Article  PubMed  CAS  Google Scholar 

  63. Clarren SK et al (1990) Neuroanatomic and neurochemical abnormalities in nonhuman primate infants exposed to weekly doses of ethanol during gestation. Alcohol Clin Exp Res 14:674–683

    Article  PubMed  CAS  Google Scholar 

  64. Burke MW, Palmour RM, Ervin FR, Ptito M (2009) Neuronal reduction in frontal cortex of primates after prenatal alcohol exposure. Neuroreport 20:13–17

    Article  PubMed  Google Scholar 

  65. Miller MW, Astley SJ, Clarren SK (1999) Number of axons in the corpus callosum of the mature Macaca nemestrina: increases caused by prenatal exposure to ethanol. J Comp Neurol 412:123–131

    Article  PubMed  CAS  Google Scholar 

  66. Sheller B, Clarren SK, Astley SJ, Sampson PD (1988) Morphometric analysis of Macaca nemestrina exposed to ethanol during gestation. Teratology 38:411–417

    Article  PubMed  CAS  Google Scholar 

  67. Lin H, Mosmann TR, Guilbert L, Tuntipopipat S, Wegmann TG (1993) Synthesis of T helper 2-type cytokines at the maternal-fetal interface. J Immunol 151:4562–4573

    PubMed  CAS  Google Scholar 

  68. Szekeres-Bartho J, Philibert D, Chaouat G (1990) Progesterone suppression of pregnancy lymphocytes is not mediated by glucocorticoid effect. Am J Reprod Immunol 23: 42–43

    PubMed  CAS  Google Scholar 

  69. Somerset DA, Zheng Y, Kilby MD, Sansom DM, Drayson MT (2004) Normal human pregnancy is associated with an elevation in the immune suppressive CD25+ CD4+ regulatory T-cell subset. Immunology 112:38–43

    Article  PubMed  CAS  Google Scholar 

  70. Aluvihare VR, Kallikourdis M, Betz AG (2004) Regulatory T cells mediate maternal tolerance to the fetus. Nat Immunol 5:266–271

    Article  PubMed  CAS  Google Scholar 

  71. Gonzalez-Quintela A, Vidal C, Gude F (2002) Alcohol-induced alterations in serum immunoglobulin e (IgE) levels in human subjects. Front Biosci 7:e234–e244

    Article  PubMed  CAS  Google Scholar 

  72. Juto P (1985) Human milk stimulates B cell function. Arch Dis Child 60:610–613

    Article  PubMed  CAS  Google Scholar 

  73. Zimecki M, Pierce-Cretel A, Spik G, Wieczorek Z (1987) Immunoregulatory properties of the proteins present in human milk. Arch Immunol Ther Exp (Warsz) 35:351–360

    CAS  Google Scholar 

  74. Steven WM, Bulloch B, Seelig LL Jr (1989) A morphometric study of the effects of ethanol consumption on lactating mammary glands of rats. Alcohol Clin Exp Res 13:209–212

    Article  PubMed  CAS  Google Scholar 

  75. Hilakivi-Clarke L et al (2004) In utero alcohol exposure increases mammary tumorigenesis in rats. Br J Cancer 90:2225–2231

    PubMed  CAS  Google Scholar 

  76. Vilaro S, Vinas O, Remesar X, Herrera E (1987) Effects of chronic ethanol consumption on lactational performance in rat: mammary gland and milk composition and pups’ growth and metabolism. Pharmacol Biochem Behav 27:333–339

    Article  PubMed  CAS  Google Scholar 

  77. Steven WM, Barron RA, Stewart GL, Seelig LL Jr (1991) The effects of maternal ethanol consumption on the distribution of leukocyte subsets in the lactating mammary gland of rats. Alcohol Alcohol 26:615–625

    PubMed  CAS  Google Scholar 

  78. Na HR, Seelig LL Jr (1994) Effect of maternal ethanol consumption on in vitro tumor necrosis factor, interleukin-6 and interleukin-2 production by rat milk and blood leukocytes. Alcohol Clin Exp Res 18:398–402

    Article  PubMed  CAS  Google Scholar 

  79. Na HR, Chervenak R, Seelig LL Jr (1993) Effects of maternal alcohol consumption on milk and blood lymphocytes and IgG antibody levels from Trichinella spiralis-infected rats. Alcohol Clin Exp Res 17:532–538

    Article  PubMed  CAS  Google Scholar 

  80. Steven WM, Stewart GL, Seelig LL (1992) The effects of maternal ethanol consumption on lactational transfer of immunity to Trichinella spiralis in rats. Alcohol Clin Exp Res 16:884–890

    Article  PubMed  CAS  Google Scholar 

  81. Seelig LL Jr, Steven WM, Stewart GL (1996) Effects of maternal ethanol consumption on the subsequent development of immunity to Trichinella spiralis in rat neonates. Alcohol Clin Exp Res 20:514–522

    Article  PubMed  Google Scholar 

  82. Steven WM, Kumar SN, Stewart GL, Seelig LL Jr (1990) The effects of ethanol consumption on the expression of immunity to Trichinella spiralis in rats. Alcohol Clin Exp Res 14:87–91

    Article  PubMed  CAS  Google Scholar 

  83. Seelig LL Jr, Steven WM, Stewart GL (1999) Second generation effects of maternal ethanol consumption on immunity to Trichinella spiralis in female rats. Alcohol Alcohol 34:520–528

    PubMed  CAS  Google Scholar 

  84. Steven WM, Stewart GL, Seelig LL Jr (1993) Effects of levamisole on ethanol-induced suppression of lactational immune transfer in rats. Alcohol Clin Exp Res 17:958–962

    Article  PubMed  CAS  Google Scholar 

  85. Becker H, Zaunschirm A, Muntean W, Domej W (1982) Fetal alcohol syndrome and malignant tumors. Wien Klin Wochenschr 94:364–365

    PubMed  CAS  Google Scholar 

  86. Chen Z et al (2005) Risk of childhood germ cell tumors in association with parental smoking and drinking. Cancer 103:1064–1071

    Article  PubMed  Google Scholar 

  87. Hornstein L, Crowe C, Gruppo R (1977) Adrenal carcinoma in child with history of fetal alcohol syndrome. Lancet 2:1292–1293

    Article  PubMed  CAS  Google Scholar 

  88. Brown LM, Pottern LM, Hoover RN (1986) Prenatal and perinatal risk factors for testicular cancer. Cancer Res 46:4812–4816

    PubMed  CAS  Google Scholar 

  89. Slater ME et al (2011) Maternal prenatal cigarette, alcohol and illicit drug use and risk of infant leukaemia: a report from the Children’s Oncology Group. Paediatr Perinat Epidemiol 25:559–565

    Article  PubMed  Google Scholar 

  90. Rudant J et al (2008) Childhood hematopoietic malignancies and parental use of tobacco and alcohol: the ESCALE study (SFCE). Cancer Causes Control 19:1277–1290

    Article  PubMed  Google Scholar 

  91. Latino-Martel P et al (2010) Maternal alcohol consumption during pregnancy and risk of childhood leukemia: systematic review and meta-analysis. Cancer Epidemiol Biomarkers Prev 19:1238–1260

    Article  PubMed  CAS  Google Scholar 

  92. Shu XO et al (1996) Parental alcohol consumption, cigarette smoking, and risk of infant leukemia: a Childrens Cancer Group study. J Natl Cancer Inst 88:24–31

    Article  PubMed  CAS  Google Scholar 

  93. van Duijn CM, van Steensel-Moll HA, Coebergh JW, van Zanen GE (1994) Risk factors for childhood acute non-lymphocytic leukemia: an association with maternal alcohol consumption during pregnancy? Cancer Epidemiol Biomarkers Prev 3:457–460

    PubMed  Google Scholar 

  94. MacArthur AC et al (2008) Risk of childhood leukemia associated with parental smoking and alcohol consumption prior to conception and during pregnancy: the cross-Canada childhood leukemia study. Cancer Causes Control 19:283–295

    Article  PubMed  Google Scholar 

  95. Infante-Rivard C, Krajinovic M, Labuda D, Sinnett D (2002) Childhood acute lymphoblastic leukemia associated with parental alcohol consumption and polymorphisms of carcinogen-metabolizing genes. Epidemiology 13:277–281

    Article  PubMed  Google Scholar 

  96. Gottesfeld Z, Trippe K, Wargovich MJ, Berkowitz AS (1992) Fetal alcohol exposure and adult tumorigenesis. Alcohol 9:465–471

    Article  PubMed  CAS  Google Scholar 

  97. Polanco TA, Crismale-Gann C, Reuhl KR, Sarkar DK, Cohick WS (2010) Fetal alcohol exposure increases mammary tumor susceptibility and alters tumor phenotype in rats. Alcohol Clin Exp Res 34:1879–1887

    Article  PubMed  CAS  Google Scholar 

  98. Penn I (1988) Tumors of the immunocompromised patient. Annu Rev Med 39:63–73

    Article  PubMed  CAS  Google Scholar 

  99. Sokol RJ et al (2007) Extreme prematurity: an alcohol-related birth effect. Alcohol Clin Exp Res 31:1031–1037

    Article  PubMed  Google Scholar 

  100. Sozo F et al (2009) Repeated ethanol exposure during late gestation alters the maturation and innate immune status of the ovine fetal lung. Am J Physiol Lung Cell Mol Physiol 296:L510–L518

    Article  PubMed  CAS  Google Scholar 

  101. Sozo F et al (2011) Effects of prenatal ethanol exposure on the lungs of postnatal lambs. Am J Physiol Lung Cell Mol Physiol 300:L139–L147

    Article  PubMed  CAS  Google Scholar 

  102. Bellanti JA, Zeligs BJ (1995) Developmental aspects of pulmonary defenses in children. Pediatr Pulmonol Suppl 11:79–80

    Article  PubMed  CAS  Google Scholar 

  103. Gauthier TW et al (2005) Fetal alcohol exposure impairs alveolar macrophage function via decreased glutathione availability. Pediatr Res 57:76–81

    Article  PubMed  CAS  Google Scholar 

  104. Ping XD, Harris FL, Brown LA, Gauthier TW (2007) In vivo dysfunction of the term alveolar macrophage after in utero ethanol exposure. Alcohol Clin Exp Res 31:308–316

    Article  PubMed  Google Scholar 

  105. Brown LA, Harris FL, Bechara R, Guidot DM (2001) Effect of chronic ethanol ingestion on alveolar type II cell: glutathione and inflammatory mediator-induced apoptosis. Alcohol Clin Exp Res 25:1078–1085

    Article  PubMed  CAS  Google Scholar 

  106. Amini SA, Dunstan RH, Dunkley PR, Murdoch RN (1996) Oxidative stress and the fetotoxicity of alcohol consumption during pregnancy. Free Radic Biol Med 21:357–365

    Article  PubMed  CAS  Google Scholar 

  107. Addolorato G et al (1997) Prenatal exposure to ethanol in rats: effects on liver energy level and antioxidant status in mothers, fetuses, and newborns. Alcohol 14:569–573

    Article  PubMed  CAS  Google Scholar 

  108. Jain A et al (1995) Glutathione metabolism in newborns: evidence for glutathione deficiency in plasma, bronchoalveolar lavage fluid, and lymphocytes in prematures. Pediatr Pulmonol 20:160–166

    Article  PubMed  CAS  Google Scholar 

  109. Seyoum G, Persaud TV (1994) In vitro effect of S-adenosyl methionine on ethanol embryopathy in the rat. Exp Toxicol Pathol 46:177–181

    Article  PubMed  CAS  Google Scholar 

  110. Devi BG, Henderson GI, Frosto TA, Schenker S (1993) Effect of ethanol on rat fetal hepatocytes: studies on cell replication, lipid peroxidation and glutathione. Hepatology 18:648–659

    Article  PubMed  CAS  Google Scholar 

  111. Heaton MB, Mitchell JJ, Paiva M (2000) Amelioration of ethanol-induced neurotoxicity in the neonatal rat central nervous system by antioxidant therapy. Alcohol Clin Exp Res 24: 512–518

    Article  PubMed  CAS  Google Scholar 

  112. Gauthier TW et al (2009) In utero ethanol exposure impairs defenses against experimental group B streptococcus in the term Guinea pig lung. Alcohol Clin Exp Res 33:300–306

    Article  PubMed  CAS  Google Scholar 

  113. Cooke RW, Drury JA (2005) Reduction of oxidative stress marker in lung fluid of preterm infants after administration of intra-tracheal liposomal glutathione. Biol Neonate 87:178–180

    Article  PubMed  CAS  Google Scholar 

  114. Samuelsson AM et al (2004) Prenatal exposure to interleukin-6 results in hypertension and increased hypothalamic-pituitary-adrenal axis activity in adult rats. Endocrinology 145: 4897–4911

    Article  PubMed  CAS  Google Scholar 

  115. Bilbo SD et al (2005) Neonatal infection-induced memory impairment after lipopolysaccharide in adulthood is prevented via caspase-1 inhibition. J Neurosci 25:8000–8009

    Article  PubMed  CAS  Google Scholar 

  116. Sittig LJ, Redei EE (2010) Paternal genetic contribution influences fetal vulnerability to maternal alcohol consumption in a rat model of fetal alcohol spectrum disorder. PLoS One 5:e10058

    Article  PubMed  CAS  Google Scholar 

  117. Hazlett LD, Barrett RP, Berk RS, Abel EL (1989) Maternal and paternal alcohol consumption increase offspring susceptibility to Pseudomonas aeruginosa ocular infection. Ophthalmic Res 21:381–387

    Article  PubMed  CAS  Google Scholar 

  118. Berk RS, Montgomery IN, Hazlett LD, Abel EL (1989) Paternal alcohol consumption: effects on ocular response and serum antibody response to Pseudomonas aeruginosa infection in offspring. Alcohol Clin Exp Res 13:795–798

    Article  PubMed  CAS  Google Scholar 

  119. Abel EL, Hazlett LS, Berk RS, Mutchnick MG (1990) Neuroimmunotoxic effects in offspring of paternal alcohol consumption. Prog Clin Biol Res 325:47–55

    PubMed  CAS  Google Scholar 

  120. Grossman CJ (1990) Are there underlying immune-neuroendocrine interactions responsible for immunological sexual dimorphism? Prog Neuroendocrinol Immunol 3:75–82

    Google Scholar 

  121. Da Silva JA (1999) Sex hormones and glucocorticoids: interactions with the immune system. Ann N Y Acad Sci 876:102–117, discussion 117–108

    Article  PubMed  Google Scholar 

  122. Martin JT (2000) Sexual dimorphism in immune function: the role of prenatal exposure to androgens and estrogens. Eur J Pharmacol 405:251–261

    Article  PubMed  CAS  Google Scholar 

  123. McGivern RF, Clancy AN, Hill MA, Noble EP (1984) Prenatal alcohol exposure alters adult expression of sexually dimorphic behavior in the rat. Science 224:896–898

    Article  PubMed  CAS  Google Scholar 

  124. Weinberg J, Sliwowska JH, Lan N, Hellemans KG (2008) Prenatal alcohol exposure: foetal programming, the hypothalamic-pituitary-adrenal axis and sex differences in outcome. J Neuroendocrinol 20:470–488

    Article  PubMed  CAS  Google Scholar 

  125. Fonzo D, Mims RB, Nelson DH (1967) Estrogen influence on pituitary and adrenal function in the rat. Endocrinology 81:29–33

    Article  PubMed  CAS  Google Scholar 

  126. Williams TD, Carter DA, Lightman SL (1985) Sexual dimorphism in the posterior pituitary response to stress in the rat. Endocrinology 116:738–740

    Article  PubMed  CAS  Google Scholar 

  127. Spinedi E, Suescun MO, Hadid R, Daneva T, Gaillard RC (1992) Effects of gonadectomy and sex hormone therapy on the endotoxin-stimulated hypothalamo-pituitary-adrenal axis: evidence for a neuroendocrine-immunological sexual dimorphism. Endocrinology 131: 2430–2436

    Article  PubMed  CAS  Google Scholar 

  128. Spinedi E, Gaillard RC, Chisari A (2002) Sexual dimorphism of neuroendocrine-immune interactions. Front Horm Res 29:91–107

    Article  PubMed  CAS  Google Scholar 

  129. Van Eden W et al (2002) Balancing the immune system: Th1 and Th2. Ann Rheum Dis 61(Suppl 2):ii25–ii28

    PubMed  Google Scholar 

  130. Lee S, Rivier C (1996) Gender differences in the effect of prenatal alcohol exposure on the hypothalamic-pituitary-adrenal axis response to immune signals. Psychoneuroendocrinology 21:145–155

    Article  PubMed  CAS  Google Scholar 

  131. Daneva T et al (1993) Transient sex-related changes in the mice hypothalamo-pituitary-adrenal (HPA) axis during the acute phase of the inflammatory process. Mediators Inflamm 2:123–127

    Article  PubMed  CAS  Google Scholar 

  132. Kirby ML, Bockman DE (1984) Neural crest and normal development: a new perspective. Anat Rec 209:1–6

    Article  PubMed  CAS  Google Scholar 

  133. Revskoy S, Halasz I, Redei E (1997) Corticotropin-releasing hormone and proopiomelanocortin gene expression is altered selectively in the male rat fetal thymus by maternal alcohol consumption. Endocrinology 138:389–396

    Article  PubMed  CAS  Google Scholar 

  134. Taylor AN et al (1993) Actions of alcohol on immunity and neoplasia in fetal alcohol exposed and adult rats. Alcohol Alcohol Suppl 2:69–74

    PubMed  CAS  Google Scholar 

  135. Chang MP, Yamaguchi DT, Yeh M, Taylor AN, Norman DC (1994) Mechanism of the impaired T-cell proliferation in adult rats exposed to alcohol in utero. Int J Immunopharmacol 16:345–357

    Article  PubMed  CAS  Google Scholar 

  136. Besedovsky HO, Rey AD (2007) Physiology of psychoneuroimmunology: a personal view. Brain Behav Immun 21:34–44

    Article  PubMed  CAS  Google Scholar 

  137. Blalock JE, Smith EM (2007) Conceptual development of the immune system as a sixth sense. Brain Behav Immun 21:23–33

    Article  PubMed  CAS  Google Scholar 

  138. Besedovsky HO, del Rey A (1996) Immune-neuro-endocrine interactions: facts and hypotheses. Endocr Rev 17:64–102

    PubMed  CAS  Google Scholar 

  139. Dhabhar FS, Miller AH, McEwen BS, Spencer RL (1996) Stress-induced changes in blood leukocyte distribution. Role of adrenal steroid hormones. J Immunol 157:1638–1644

    PubMed  CAS  Google Scholar 

  140. Ulrich-Lai YM, Herman JP (2009) Neural regulation of endocrine and autonomic stress responses. Nat Rev Neurosci 10:397–409

    Article  PubMed  CAS  Google Scholar 

  141. Jankord R, Herman JP (2008) Limbic regulation of hypothalamo-pituitary-adrenocortical function during acute and chronic stress. Ann N Y Acad Sci 1148:64–73

    Article  PubMed  Google Scholar 

  142. Dallman MF et al (1987) Regulation of ACTH secretion: variations on a theme of B. Recent Prog Horm Res 43:113–173

    PubMed  CAS  Google Scholar 

  143. Rivier CL, Plotsky PM (1986) Mediation by corticotropin releasing factor (CRF) of adenohypophysial hormone secretion. Annu Rev Physiol 48:475–494

    Article  PubMed  CAS  Google Scholar 

  144. Jones MT, Gillham B (1988) Factors involved in the regulation of adrenocorticotropic hormone/beta-lipotropic hormone. Physiol Rev 68:743–818

    PubMed  CAS  Google Scholar 

  145. Sapolsky RM, Romero LM, Munck AU (2000) How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 21:55–89

    Article  PubMed  CAS  Google Scholar 

  146. De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M (1998) Brain corticosteroid receptor balance in health and disease. Endocr Rev 19:269–301

    Article  PubMed  Google Scholar 

  147. McEwen BS, Stellar E (1993) Stress and the individual. Mechanisms leading to disease. Arch Intern Med 153:2093–2101

    Article  PubMed  CAS  Google Scholar 

  148. Weinberg J, Bezio S (1987) Alcohol-induced changes in pituitary-adrenal activity during pregnancy. Alcohol Clin Exp Res 11:274–280

    Article  PubMed  CAS  Google Scholar 

  149. Weinberg J, Gallo PV (1982) Prenatal ethanol exposure: pituitary-adrenal activity in pregnant dams and offspring. Neurobehav Toxicol Teratol 4:515–520

    PubMed  CAS  Google Scholar 

  150. Weinberg J (1989) Prenatal ethanol exposure alters adrenocortical development of offspring. Alcohol Clin Exp Res 13:73–83

    Article  PubMed  CAS  Google Scholar 

  151. Eguchi Y (1969) Interrelationships between the foetal and maternal hypophysial-adrenal axes in rats and mice. In: Bajusz E (ed) Physiology and pathology of adaptation mechanisms. Pergamon Press, New York, pp 3–27

    Google Scholar 

  152. Kakihana R, Butte JC, Moore JA (1980) Endocrine effects of maternal alcoholization: plasma and brain testosterone, dihydrotestosterone, estradiol, and corticosterone. Alcohol Clin Exp Res 4:57–61

    Article  PubMed  CAS  Google Scholar 

  153. Taylor AN, Branch BJ, Kokka N, Poland RE (1983) Neonatal and long-term neuroendocrine effects of fetal alcohol exposure. Monogr Neural Sci 9:140–152

    PubMed  CAS  Google Scholar 

  154. Angelogianni P, Gianoulakis C (1989) Prenatal exposure to ethanol alters the ontogeny of the beta-endorphin response to stress. Alcohol Clin Exp Res 13:564–571

    Article  PubMed  CAS  Google Scholar 

  155. Taylor AN, Branch BJ, Nelson LR, Lane LA, Poland RE (1986) Prenatal ethanol and ontogeny of pituitary-adrenal responses to ethanol and morphine. Alcohol 3:255–259

    Article  PubMed  CAS  Google Scholar 

  156. Aird F, Halasz I, Redei E (1997) Ontogeny of hypothalamic corticotropin-releasing factor and anterior pituitary pro-opiomelanocortin expression in male and female offspring of alcohol-exposed and adrenalectomized dams. Alcohol Clin Exp Res 21:1560–1566

    Article  PubMed  CAS  Google Scholar 

  157. Taylor AN, Branch BJ, Van Zuylen JE, Redei E (1988) Maternal alcohol consumption and stress responsiveness in offspring. Adv Exp Med Biol 245:311–317

    PubMed  CAS  Google Scholar 

  158. Lee S, Imaki T, Vale W, Rivier C (1990) Effect of prenatal exposure to ethanol on the activity of the hypothalamic-pituitary-adrenal axis of the offspring: importance of the time of exposure to ethanol and possible modulating mechanisms. Mol Cell Neurosci 1:168–177

    Article  PubMed  CAS  Google Scholar 

  159. Weinberg J (1993) Neuroendocrine effects of prenatal alcohol exposure. Ann N Y Acad Sci 697:86–96

    Article  PubMed  CAS  Google Scholar 

  160. Lee S, Schmidt D, Tilders F, Rivier C (2000) Increased activity of the hypothalamic-pituitary-adrenal axis of rats exposed to alcohol in utero: role of altered pituitary and hypothalamic function. Mol Cell Neurosci 16:515–528

    Article  PubMed  CAS  Google Scholar 

  161. Glavas MM, Ellis L, Yu WK, Weinberg J (2007) Effects of prenatal ethanol exposure on basal limbic-hypothalamic-pituitary-adrenal regulation: role of corticosterone. Alcohol Clin Exp Res 31:1598–1610

    Article  PubMed  CAS  Google Scholar 

  162. Schneider ML, Moore CF, Kraemer GW (2004) Moderate level alcohol during pregnancy, prenatal stress, or both and limbic-hypothalamic-pituitary-adrenocortical axis response to stress in rhesus monkeys. Child Dev 75:96–109

    Article  PubMed  Google Scholar 

  163. Jacobson SW, Bihun JT, Chiodo LM (1999) Effects of prenatal alcohol and cocaine exposure on infant cortisol levels. Dev Psychopathol 11:195–208

    Article  PubMed  CAS  Google Scholar 

  164. Ramsay DS, Bendersky MI, Lewis M (1996) Effect of prenatal alcohol and cigarette exposure on two- and six-month-old infants’ adrenocortical reactivity to stress. J Pediatr Psychol 21:833–840

    Article  PubMed  CAS  Google Scholar 

  165. Haley DW, Handmaker NS, Lowe J (2006) Infant stress reactivity and prenatal alcohol exposure. Alcohol Clin Exp Res 30:2055–2064

    Article  PubMed  Google Scholar 

  166. Weinberg J (1988) Hyperresponsiveness to stress: differential effects of prenatal ethanol on males and females. Alcohol Clin Exp Res 12:647–652

    Article  PubMed  CAS  Google Scholar 

  167. Weinberg J (1992) Prenatal ethanol effects: sex differences in offspring stress responsiveness. Alcohol 9:219–223

    Article  PubMed  CAS  Google Scholar 

  168. Halasz I, Aird F, Li L, Prystowsky MB, Redei E (1993) Sexually dimorphic effects of alcohol exposure in utero on neuroendocrine and immune functions in chronic alcohol-exposed adult rats. Mol Cell Neurosci 4:343–353

    Article  PubMed  CAS  Google Scholar 

  169. Kim CK, Turnbull AV, Lee SY, Rivier CL (1999) Effects of prenatal exposure to alcohol on the release of adenocorticotropic hormone, corticosterone, and proinflammatory cytokines. Alcohol Clin Exp Res 23:52–59

    Article  PubMed  CAS  Google Scholar 

  170. Weinberg J, Taylor AN, Gianoulakis C (1996) Fetal ethanol exposure: hypothalamic-pituitary-adrenal and beta-endorphin responses to repeated stress. Alcohol Clin Exp Res 20:122–131

    Article  PubMed  CAS  Google Scholar 

  171. Taylor AN, Branch BJ, Liu SH, Kokka N (1982) Long-term effects of fetal ethanol exposure on pituitary-adrenal response to stress. Pharmacol Biochem Behav 16:585–589

    Article  PubMed  CAS  Google Scholar 

  172. Slone JL, Redei EE (2002) Maternal alcohol and adrenalectomy: asynchrony of stress response and forced swim behavior. Neurotoxicol Teratol 24:173–178

    Article  PubMed  CAS  Google Scholar 

  173. Lee S, Rivier C (1992) Administration of corticosterone to pregnant adrenalectomized dams does not alter the hypothalamic-pituitary-adrenal axis’ activity of the offspring. Mol Cell Neurosci 3:118–123

    Article  PubMed  CAS  Google Scholar 

  174. Redei E, Halasz I, Li LF, Prystowsky MB, Aird F (1993) Maternal adrenalectomy alters the immune and endocrine functions of fetal alcohol-exposed male offspring. Endocrinology 133:452–460

    Article  PubMed  CAS  Google Scholar 

  175. Sinha P, Halasz I, Choi JF, McGivern RF, Redei E (1997) Maternal adrenalectomy eliminates a surge of plasma dehydroepiandrosterone in the mother and attenuates the prenatal testosterone surge in the male fetus. Endocrinology 138:4792–4797

    Article  PubMed  CAS  Google Scholar 

  176. Tritt SH, Tio DL, Brammer GL, Taylor AN (1993) Adrenalectomy but not adrenal demedullation during pregnancy prevents the growth-retarding effects of fetal alcohol exposure. Alcohol Clin Exp Res 17:1281–1289

    Article  PubMed  CAS  Google Scholar 

  177. Taylor AN, Tritt SH, Tio DL, Romeo HE, Yirmiya R (2002) Maternal adrenalectomy abrogates the effect of fetal alcohol exposure on the interleukin-1beta-induced febrile response: gender differences. Neuroendocrinology 76:185–192

    Article  PubMed  CAS  Google Scholar 

  178. Giberson PK, Weinberg J (1995) Effects of prenatal ethanol exposure and stress in adulthood on lymphocyte populations in rats. Alcohol Clin Exp Res 19:1286–1294

    Article  PubMed  CAS  Google Scholar 

  179. Cunningham ET Jr, De Souza EB (1993) Interleukin 1 receptors in the brain and endocrine tissues. Immunol Today 14:171–176

    Article  PubMed  CAS  Google Scholar 

  180. Zalcman S et al (1994) Cytokine-specific central monoamine alterations induced by interleukin-1, -2 and -6. Brain Res 643:40–49

    Article  PubMed  CAS  Google Scholar 

  181. Dunn AJ, Wang J (1995) Cytokine effects on CNS biogenic amines. Neuroimmunomodulation 2:319–328

    Article  PubMed  CAS  Google Scholar 

  182. Rivier C (1993) Effect of peripheral and central cytokines on the hypothalamic-pituitary-adrenal axis of the rat. Ann N Y Acad Sci 697:97–105

    Article  PubMed  CAS  Google Scholar 

  183. Watkins LR, Maier SF (2000) The pain of being sick: implications of immune-to-brain communication for understanding pain. Annu Rev Psychol 51:29–57

    Article  PubMed  CAS  Google Scholar 

  184. Dantzer R (2001) Cytokine-induced sickness behavior: mechanisms and implications. Ann N Y Acad Sci 933:222–234

    Article  PubMed  CAS  Google Scholar 

  185. Hetier E et al (1988) Brain macrophages synthesize interleukin-1 and interleukin-1 mRNAs in vitro. J Neurosci Res 21:391–397

    Article  PubMed  CAS  Google Scholar 

  186. Sebire G et al (1993) In vitro production of IL-6, IL-1 beta, and tumor necrosis factor-alpha by human embryonic microglial and neural cells. J Immunol 150:1517–1523

    PubMed  CAS  Google Scholar 

  187. Suda T et al (1990) Interleukin-1 stimulates corticotropin-releasing factor gene expression in rat hypothalamus. Endocrinology 126:1223–1228

    Article  PubMed  CAS  Google Scholar 

  188. Chover-Gonzalez AJ, Lightman SL, Harbuz MS (1994) An investigation of the effects of interleukin-1 beta on plasma arginine vasopressin in the rat: role of adrenal steroids. J Endocrinol 142:361–366

    Article  PubMed  CAS  Google Scholar 

  189. Kehrer P, Turnill D, Dayer JM, Muller AF, Gaillard RC (1988) Human recombinant interleukin-1 beta and -alpha, but not recombinant tumor necrosis factor alpha stimulate ACTH release from rat anterior pituitary cells in vitro in a prostaglandin E2 and cAMP independent manner. Neuroendocrinology 48:160–166

    Article  PubMed  CAS  Google Scholar 

  190. Sharp BM et al (1989) Tumor necrosis factor-alpha is a potent ACTH secretagogue: comparison to interleukin-1 beta. Endocrinology 124:3131–3133

    Article  PubMed  CAS  Google Scholar 

  191. Lyson K, McCann SM (1991) The effect of interleukin-6 on pituitary hormone release in vivo and in vitro. Neuroendocrinology 54:262–266

    Article  PubMed  CAS  Google Scholar 

  192. Taylor AN, Tio DL, Yirmiya R (1999) Fetal alcohol exposure attenuates interleukin-1beta-induced fever: neuroimmune mechanisms. J Neuroimmunol 99:44–52

    Article  PubMed  CAS  Google Scholar 

  193. Taylor AN, Tio DL, Heng NS, Yirmiya R (2002) Alcohol consumption attenuates febrile responses to lipopolysaccharide and interleukin-1 beta in male rats. Alcohol Clin Exp Res 26:44–52

    PubMed  CAS  Google Scholar 

  194. Ylikorkala O, Stenman UH, Halmesmaki E (1988) Testosterone, androstenedione, dehydroepiandrosterone sulfate, and sex-hormone-binding globulin in pregnant alcohol abusers. Obstet Gynecol 71:731–735

    PubMed  CAS  Google Scholar 

  195. Yirmiya R, Pilati ML, Chiappelli F, Taylor AN (1993) Fetal alcohol exposure attenuates lipopolysaccharide-induced fever in rats. Alcohol Clin Exp Res 17:906–910

    Article  PubMed  CAS  Google Scholar 

  196. Yirmiya R, Tio DL, Taylor AN (1996) Effects of fetal alcohol exposure on fever, sickness behavior, and pituitary-adrenal activation induced by interleukin-1 beta in young adult rats. Brain Behav Immun 10:205–220

    Article  PubMed  CAS  Google Scholar 

  197. Lee S, Rivier C (1993) Prenatal alcohol exposure blunts interleukin-1-induced ACTH and beta-endorphin secretion by immature rats. Alcohol Clin Exp Res 17:940–945

    Article  PubMed  CAS  Google Scholar 

  198. Chiappelli F et al (1997) Fetal alcohol exposure augments the blunting of tumor necrosis factor production in vitro resulting from in vivo priming with lipopolysaccharide in young adult male but not female rats. Alcohol Clin Exp Res 21:1542–1546

    Article  PubMed  CAS  Google Scholar 

  199. Yirmiya R, Chiappelli F, Tio DL, Tritt SH, Taylor AN (1998) Effects of prenatal alcohol and pair feeding on lipopolysaccharide-induced secretion of TNF-alpha and corticosterone. Alcohol 15:327–335

    Article  PubMed  CAS  Google Scholar 

  200. Vink J, Auth J, Abebe DT, Brenneman DE, Spong CY (2005) Novel peptides prevent alcohol-induced spatial learning deficits and proinflammatory cytokine release in a mouse model of fetal alcohol syndrome. Am J Obstet Gynecol 193:825–829

    Article  PubMed  CAS  Google Scholar 

  201. Crews FT et al (2006) Cytokines and alcohol. Alcohol Clin Exp Res 30:720–730

    Article  PubMed  CAS  Google Scholar 

  202. Szabo G, Mandrekar P (2009) A recent perspective on alcohol, immunity, and host defense. Alcohol Clin Exp Res 33:220–232

    Article  PubMed  CAS  Google Scholar 

  203. Liverman CS et al (2006) Altered expression of pro-inflammatory and developmental genes in the fetal brain in a mouse model of maternal infection. Neurosci Lett 399:220–225

    Article  PubMed  CAS  Google Scholar 

  204. Jonakait GM (2007) The effects of maternal inflammation on neuronal development: possible mechanisms. Int J Dev Neurosci 25:415–425

    Article  PubMed  CAS  Google Scholar 

  205. Meyer U, Feldon J, Yee BK (2009) A review of the fetal brain cytokine imbalance hypothesis of schizophrenia. Schizophr Bull 35:959–972

    Article  PubMed  Google Scholar 

  206. Gayle DA et al (2004) Maternal LPS induces cytokines in the amniotic fluid and corticotropin releasing hormone in the fetal rat brain. Am J Physiol Regul Integr Comp Physiol 286:R1024–R1029

    Article  PubMed  CAS  Google Scholar 

  207. Zaretsky MV, Alexander JM, Byrd W, Bawdon RE (2004) Transfer of inflammatory cytokines across the placenta. Obstet Gynecol 103:546–550

    Article  PubMed  CAS  Google Scholar 

  208. Aaltonen R, Heikkinen T, Hakala K, Laine K, Alanen A (2005) Transfer of proinflammatory cytokines across term placenta. Obstet Gynecol 106:802–807

    Article  PubMed  CAS  Google Scholar 

  209. Dahlgren J, Samuelsson AM, Jansson T, Holmang A (2006) Interleukin-6 in the maternal circulation reaches the rat fetus in mid-gestation. Pediatr Res 60:147–151

    Article  PubMed  CAS  Google Scholar 

  210. Kaminen-Ahola N, Ahola A, Maga M, Mallitt KA, Fahey P, Cox TC, Whitelaw E, Chong S. Maternal ethanol consumption alters the epigenotype and the phenotype of offspring in a mouse model. PLoS Genet. 6:e1000811, 2010

    Article  PubMed  CAS  Google Scholar 

  211. Pang Y, Cai Z, Rhodes PG (2003) Disturbance of oligodendrocyte development, hypomyelination and white matter injury in the neonatal rat brain after intracerebral injection of lipopolysaccharide. Brain Res Dev Brain Res 140:205–214

    Article  PubMed  CAS  Google Scholar 

  212. Ader R (1998) Psychoneuroimmunology. ILAR J 39:27–29

    PubMed  Google Scholar 

  213. Schwarz JM, Bilbo SD (2012) The immune system and the developing brain. In: McCarthy MM (ed) The developing brain. Morgan & Claypool Life Sciences, San Rafael, pp 1–118

    Google Scholar 

  214. Bajetto A, Bonavia R, Barbero S, Florio T, Schettini G (2001) Chemokines and their receptors in the central nervous system. Front Neuroendocrinol 22:147–184

    Article  PubMed  CAS  Google Scholar 

  215. Nakashima K, Taga T (2002) Mechanisms underlying cytokine-mediated cell-fate regulation in the nervous system. Mol Neurobiol 25:233–244

    Article  PubMed  CAS  Google Scholar 

  216. Ling EA, Wong WC (1993) The origin and nature of ramified and amoeboid microglia: a historical review and current concepts. Glia 7:9–18

    Article  PubMed  CAS  Google Scholar 

  217. Fujita S, Tsuchihashi Y, Kitamura T (1981) Origin, morphology and function of the microglia. Prog Clin Biol Res 59A:141–169

    PubMed  CAS  Google Scholar 

  218. Ashwell K (1990) Microglia and cell death in the developing mouse cerebellum. Brain Res Dev Brain Res 55:219–230

    Article  PubMed  CAS  Google Scholar 

  219. Elkabes S, DiCicco-Bloom EM, Black IB (1996) Brain microglia/macrophages express neurotrophins that selectively regulate microglial proliferation and function. J Neurosci 16:2508–2521

    PubMed  CAS  Google Scholar 

  220. Marin-Teva JL et al (2004) Microglia promote the death of developing Purkinje cells. Neuron 41:535–547

    Article  PubMed  CAS  Google Scholar 

  221. Town T, Nikolic V, Tan J (2005) The microglial “activation” continuum: from innate to ­adaptive responses. J Neuroinflammation 2:24

    Article  PubMed  CAS  Google Scholar 

  222. Zhang X et al (2012) Prenatal alcohol exposure alters the course and severity of adjuvant-induced arthritis in female rats. Brain Behav Immun 26:439–450

    Article  PubMed  CAS  Google Scholar 

  223. Harbuz MS, Rees RG, Lightman SL (1993) HPA axis responses to acute stress and adrenalectomy during adjuvant-induced arthritis in the rat. Am J Physiol 264:R179–R185

    PubMed  CAS  Google Scholar 

  224. Chover-Gonzalez AJ et al (1999) Effects of stress on susceptibility and severity of inflammation in adjuvant-induced arthritis. Ann N Y Acad Sci 876:276–286

    Article  PubMed  CAS  Google Scholar 

  225. Chover-Gonzalez AJ, Jessop DS, Tejedor-Real P, Gibert-Rahola J, Harbuz MS (2000) Onset and severity of inflammation in rats exposed to the learned helplessness paradigm. Rheumatology (Oxford) 39:764–771

    Article  CAS  Google Scholar 

  226. Bomholt SF, Harbuz MS, Blackburn-Munro G, Blackburn-Munro RE (2004) Involvement and role of the hypothalamo-pituitary-adrenal (HPA) stress axis in animal models of chronic pain and inflammation. Stress 7:1–14

    Article  PubMed  CAS  Google Scholar 

  227. Del Rey A et al (2010) When immune-neuro-endocrine interactions are disrupted: experimentally induced arthritis as an example. Neuroimmunomodulation 17:165–168

    Article  PubMed  CAS  Google Scholar 

  228. Owen D, Andrews MH, Matthews SG (2005) Maternal adversity, glucocorticoids and programming of neuroendocrine function and behaviour. Neurosci Biobehav Rev 29:209–226

    Article  PubMed  CAS  Google Scholar 

  229. Welberg LA, Seckl JR (2001) Prenatal stress, glucocorticoids and the programming of the brain. J Neuroendocrinol 13:113–128

    Article  PubMed  CAS  Google Scholar 

  230. Liu L, Li A, Matthews SG (2001) Maternal glucocorticoid treatment programs HPA regulation in adult offspring: sex-specific effects. Am J Physiol Endocrinol Metab 280:E729–E739

    PubMed  CAS  Google Scholar 

  231. Matthews SG (2002) Early programming of the hypothalamo-pituitary-adrenal axis. Trends Endocrinol Metab 13:373–380

    Article  PubMed  CAS  Google Scholar 

  232. Colebatch AN, Edwards CJ (2011) The influence of early life factors on the risk of developing rheumatoid arthritis. Clin Exp Immunol 163:11–16

    Article  PubMed  CAS  Google Scholar 

  233. McEwen BS (1998) Stress, adaptation, and disease. Allostasis and allostatic load. Ann N Y Acad Sci 840:33–44

    Article  PubMed  CAS  Google Scholar 

  234. Weaver IC et al (2004) Epigenetic programming by maternal behavior. Nat Neurosci 7:847–854

    Article  PubMed  CAS  Google Scholar 

  235. Haycock PC (2009) Fetal alcohol spectrum disorders: the epigenetic perspective. Biol Reprod 81:607–617

    Article  PubMed  CAS  Google Scholar 

  236. Kobor M, Weinberg J (2011) Focus on: epigenetics and fetal alcohol spectrum disorders. Alcohol Res Health 34:29–37

    Google Scholar 

  237. Livy DJ, Maier SE, West JR (2004) Long-term alcohol exposure prior to conception results in lower fetal body weights. Birth Defects Res B Dev Reprod Toxicol 71:135–141

    Article  PubMed  CAS  Google Scholar 

  238. Haycock PC, Ramsay M (2009) Exposure of mouse embryos to ethanol during preimplantation development: effect on DNA methylation in the h19 imprinting control region. Biol Reprod 81:618–627

    Article  PubMed  CAS  Google Scholar 

  239. Garro AJ, McBeth DL, Lima V, Lieber CS (1991) Ethanol consumption inhibits fetal DNA methylation in mice: implications for the fetal alcohol syndrome. Alcohol Clin Exp Res 15:395–398

    Article  PubMed  CAS  Google Scholar 

  240. Guo W et al (2011) Alcohol exposure decreases CREB binding protein expression and histone acetylation in the developing cerebellum. PLoS One 6:e19351

    Article  PubMed  CAS  Google Scholar 

  241. Mathews HL, Janusek LW (2011) Epigenetics and psychoneuroimmunology: mechanisms and models. Brain Behav Immun 25:25–39

    Article  PubMed  Google Scholar 

  242. Cuddapah S, Barski A, Zhao K (2010) Epigenomics of T cell activation, differentiation, and memory. Curr Opin Immunol 22:341–347

    Article  PubMed  CAS  Google Scholar 

  243. Martino DJ, Prescott SL (2010) Silent mysteries: epigenetic paradigms could hold the key to conquering the epidemic of allergy and immune disease. Allergy 65:7–15

    Article  PubMed  CAS  Google Scholar 

  244. Martino D, Prescott S (2011) Epigenetics and prenatal influences on asthma and allergic ­airways disease. Chest 139:640–647

    Article  PubMed  CAS  Google Scholar 

  245. Miller RL (2008) Prenatal maternal diet affects asthma risk in offspring. J Clin Invest 118:3265–3268

    PubMed  CAS  Google Scholar 

  246. Trenkmann M, Brock M, Ospelt C, Gay S (2010) Epigenetics in rheumatoid arthritis. Clin Rev Allergy Immunol 39:10–19

    Article  PubMed  CAS  Google Scholar 

  247. Strietholt S, Maurer B, Peters MA, Pap T, Gay S (2008) Epigenetic modifications in rheumatoid arthritis. Arthritis Res Ther 10:219

    Article  PubMed  CAS  Google Scholar 

  248. Chen P, Jiang T, Ouyang J, Cui Y, Chen Y (2009) Epigenetic programming of diverse glucocorticoid response and inflammatory/immune-mediated disease. Med Hypotheses 73:657–658

    Article  PubMed  CAS  Google Scholar 

  249. Szyf M (2010) Epigenetic therapeutics in autoimmune disease. Clin Rev Allergy Immunol 39:62

    Article  PubMed  CAS  Google Scholar 

  250. Holladay SD, Smialowicz RJ, (2000). Development of the murine and human immune system: differential effects of immunotoxicants depend on time of exposure. Environ Health Perspect 108 Suppl 3:463–473

    Article  PubMed  CAS  Google Scholar 

  251. Kumar SN, Stewart GL, Steven WM, Seelig LL (1989) Maternal to neonatal transmission of T-cell mediated immunity to Trichinella spiralis during lactation. Immunology 68(1):87–92

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

The research from our laboratory reported in this review is supported by grants NIH/NIAAA R37 AA007789 to JW and R21 AA AA016683 to JW (CoIs: S. Innis, A. Devlin); NIH/NIMH R24 MH081797 (Project 2) to JW (CoIs: M. Kobor, G.G. Meadows). TB is supported by a fellowship from the National Sciences and Engineering Research Council (NSERC CGS-D) and a University Graduate Fellowship. Versions of some sections of this chapter have appeared previously in published work, as cited.

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Bodnar, T., Weinberg, J. (2013). Prenatal Alcohol Exposure: Impact on Neuroendocrine–Neuroimmune Networks. In: Cui, C., Grandison, L., Noronha, A. (eds) Neural-Immune Interactions in Brain Function and Alcohol Related Disorders. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-4729-0_10

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