Effects of prenatal infection on brain development and behavior: A review of findings from animal models

Brain, Behavior, and Immunity - Tập 24 Số 6 - Trang 881-897 - 2010
Patricia Boksa1
1Department of Psychiatry, McGill University, Douglas Mental Health University Institute, Montreal, Verdun, Quebec, Canada.

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Adams, 1993, Epidemiological evidence that maternal influenza contributes to the aetiology of schizophrenia. An analysis of Scottish, English, and Danish data, Br. J. Psychiatry, 163, 522, 10.1192/bjp.163.4.522

Aderem, 2000, Toll-like receptors in the induction of the innate immune response, Nature, 406, 782, 10.1038/35021228

Akarsu, 2007, Escherichia coli lipopolysaccharides produce serotype-specific hypothermic response in biotelemetered rats, Am. J. Physiol., 292, R1846

Aleman, 2003, Sex differences in the risk of schizophrenia: evidence from meta-analysis, Arch. Gen. Psychiatry, 60, 565, 10.1001/archpsyc.60.6.565

Aronsson, 2002, Persistence of viral RNA in the brain of offspring to mice infected with influenza A/WSN/33 virus during pregnancy, J. Neurovirol., 8, 353, 10.1080/13550280290100480

Ashdown, 2006, The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia, Mol. Psychiatry, 11, 47, 10.1038/sj.mp.4001748

Ashdown, 2007, Interleukin-1 receptor antagonist as a modulator of gender differences in the febrile response to lipopolysaccharide in rats, Am. J. Physiol., 292, R1667

Asp, 2005, Gene expression changes in brains of mice exposed to a maternal virus infection, Neuroreport, 16, 1111, 10.1097/00001756-200507130-00016

Avishai-Eliner, 2002, Stressed-out, or in (utero)?, Trends Neurosci., 25, 518, 10.1016/S0166-2236(02)02241-5

Babulas, 2006, Prenatal exposure to maternal genital and reproductive infections and adult schizophrenia, Am. J. Psychiatry, 163, 927, 10.1176/ajp.2006.163.5.927

Baharnoori, 2009, Prenatal immune challenge induces developmental changes in the morphology of pyramidal neurons of the prefrontal cortex and hippocampus in rats, Schizophr. Res., 107, 99, 10.1016/j.schres.2008.10.003

Bakos, 2004, Prenatal immune challenge affects growth, behavior, and brain dopamine in offspring, Ann. N. Y. Acad. Sci., 1018, 281, 10.1196/annals.1296.033

Balasingam, 1994, Reactive astrogliosis in the neonatal mouse brain and its modulation by cytokines, J. Neurosci., 14, 846, 10.1523/JNEUROSCI.14-02-00846.1994

Barr, 1990, Exposure to influenza epidemics during gestation and adult schizophrenia. A 40-year study, Arch. Gen. Psychiatry, 47, 869, 10.1001/archpsyc.1990.01810210077012

Battle, 1999, Seasonality and infectious disease in schizophrenia: the birth hypothesis revisited, J. Psychiatr. Res., 33, 501, 10.1016/S0022-3956(99)00022-9

Begg, 2007, Suppression of endotoxin-induced fever in near-term pregnant rats is mediated by brain nitric oxide, Am. J. Physiol., 292, R2174

Borrell, 2002, Prenatal immune challenge disrupts sensorimotor gating in adult rats. Implications for the etiopathogenesis of schizophrenia, Neuropsychopharmacology, 26, 204, 10.1016/S0893-133X(01)00360-8

Brown, 2010, Prenatal infection and schizophrenia: a review of epidemiologic and translational studies, Am. J. Psychiatry, 167, 261, 10.1176/appi.ajp.2009.09030361

Brown, 2002, In utero infection and adult schizophrenia, Ment. Retard. Dev. Disabil. Res. Rev., 8, 51, 10.1002/mrdd.10004

Brown, 2000, Maternal exposure to respiratory infections and adult schizophrenia spectrum disorders: a prospective birth cohort study, Schizophr. Bull., 26, 287, 10.1093/oxfordjournals.schbul.a033453

Brown, 2004, Serologic evidence of prenatal influenza in the etiology of schizophrenia, Arch. Gen. Psychiatry, 61, 774, 10.1001/archpsyc.61.8.774

Brown, 2005, Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring, Am. J. Psychiatry, 162, 767, 10.1176/appi.ajp.162.4.767

Brown, 2009, Prenatal exposure to maternal infection and executive dysfunction in adult schizophrenia, Am. J. Psychiatry, 166, 683, 10.1176/appi.ajp.2008.08010089

Buka, 2008, Maternal exposure to herpes simplex virus and risk of psychosis among adult offspring, Biol. Psychiatry, 63, 809, 10.1016/j.biopsych.2007.09.022

Byrne, 2007, Obstetric conditions and risk of first admission with schizophrenia: a Danish national register based study, Schizophr. Res., 97, 51, 10.1016/j.schres.2007.07.018

Cai, 2000, Cytokine induction in fetal rat brains and brain injury in neonatal rats after maternal lipopolysaccharide administration, Pediatr. Res., 47, 64, 10.1203/00006450-200001000-00013

Cambonie, 2004, Prenatal infection obliterates glutamate-related protection against free hydroxyl radicals in neonatal rat brain, J. Neurosci. Res., 75, 125, 10.1002/jnr.10823

Carey, 2003, Zinc treatment prevents lipopolysaccharide-induced teratogenicity in mice, Birth Defects Res. A Clin. Mol. Teratol., 67, 240, 10.1002/bdra.10035

Chao, 1994, Tumor necrosis factor-alpha potentiates glutamate neurotoxicity in human fetal brain cultures, Dev. Neurosci., 16, 171, 10.1159/000112104

Chen, 2005, Differential expression of cytokines in the brain and serum during endotoxin tolerance, J. Neuroimmunol., 163, 53, 10.1016/j.jneuroim.2005.02.012

Chen, 2006, Ascorbic acid protects against lipopolysaccharide-induced intra-uterine fetal death and intra-uterine growth retardation in mice, Toxicology, 217, 39, 10.1016/j.tox.2005.08.010

Chess, 1977, Follow-up report on autism in congenital rubella, J. Autism Child. Schizophr., 7, 69, 10.1007/BF01531116

Chua, 2006, Dietary zinc supplementation ameliorates LPS-induced teratogenicity in mice, Pediatr. Res., 59, 355, 10.1203/01.pdr.0000199906.37619.9c

Ciaranello, 1995, The neurobiology of infantile autism, Annu. Rev. Neurosci., 18, 101, 10.1146/annurev.ne.18.030195.000533

Clancy, 2007, Extrapolating brain development from experimental species to humans, Neurotoxicology, 28, 931, 10.1016/j.neuro.2007.01.014

Clark, 2008, Antenatal antecedents and the impact of obstetric care in the etiology of cerebral palsy, Clin. Obstet. Gynecol., 51, 775, 10.1097/GRF.0b013e3181870994

Clarke, 2009, Evidence for an interaction between familial liability and prenatal exposure to infection in the causation of schizophrenia, Am. J. Psychiatry, 166, 1025, 10.1176/appi.ajp.2009.08010031

Coyle, 2009, Maternal dietary zinc supplementation prevents aberrant behaviour in an object recognition task in mice offspring exposed to LPS in early pregnancy, Behav. Brain Res., 197, 210, 10.1016/j.bbr.2008.08.022

Cui, 2009, Effects of prenatal immune activation on hippocampal neurogenesis in the rat, Schizophr. Res., 113, 288, 10.1016/j.schres.2009.05.003

Dahlgren, 2006, Interleukin-6 in the maternal circulation reaches the rat fetus in mid-gestation, Pediatr. Res., 60, 147, 10.1203/01.pdr.0000230026.74139.18

Derijk, 1994, Hypothermia to endotoxin involves reduced thermogenesis, macrophage-dependent mechanisms, and prostaglandins, Am. J. Physiol., 266, R1

Deverman, 2009, Cytokines and CNS development, Neuron, 64, 61, 10.1016/j.neuron.2009.09.002

Doughty, 2006, Activation of common antiviral pathways can potentiate inflammatory responses to septic shock, Shock, 26, 187, 10.1097/01.shk.0000223129.79759.74

Ebert, 2005, Prenatal exposure to influenza and the risk of subsequent development of schizophrenia, Isr. Med. Assoc. J., 7, 35

Ellman, 2009, Cognitive functioning prior to the onset of psychosis: the role of fetal exposure to serologically determined influenza infection, Biol. Psychiatry, 65, 1040, 10.1016/j.biopsych.2008.12.015

Fatemi, 1998, Differential expression of synaptosome-associated protein 25kDa [SNAP-25] in hippocampi of neonatal mice following exposure to human influenza virus in utero, Brain Res., 800, 1, 10.1016/S0006-8993(98)00450-8

Fatemi, 1999, Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prenatally infected neonatal mice, Mol. Psychiatry, 4, 145, 10.1038/sj.mp.4000520

Fatemi, 2002, Prenatal viral infection leads to pyramidal cell atrophy and macrocephaly in adulthood: implications for genesis of autism and schizophrenia, Cell. Mol. Neurobiol., 22, 25, 10.1023/A:1015337611258

Fatemi, 2002, Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice, Mol. Psychiatry, 7, 633, 10.1038/sj.mp.4001046

Fatemi, 2005, Prenatal viral infection in mouse causes differential expression of genes in brains of mouse progeny: a potential animal model for schizophrenia and autism, Synapse, 57, 91, 10.1002/syn.20162

Fatemi, 2008, Maternal infection leads to abnormal gene regulation and brain atrophy in mouse offspring: implications for genesis of neurodevelopmental disorders, Schizophr. Res., 99, 56, 10.1016/j.schres.2007.11.018

Fatemi, 2008, Viral regulation of aquaporin 4, connexin 43, microcephalin and nucleolin, Schizophr. Res., 98, 163, 10.1016/j.schres.2007.09.031

Fatemi, 2009, Abnormal expression of myelination genes and alterations in white matter fractional anisotropy following prenatal viral influenza infection at E16 in mice, Schizophr. Res., 112, 46, 10.1016/j.schres.2009.04.014

Fatemi, 2009, Prenatal viral infection of mice at E16 causes changes in gene expression in hippocampi of the offspring, Eur. Neuropsychopharmacol., 19, 648, 10.1016/j.euroneuro.2009.03.004

Feldberg, 1975, Prostaglandins, endotoxin and lipid A on body temperature in rats, J. Physiol., 249, 601, 10.1113/jphysiol.1975.sp011033

Fofie, 2003, Influence of pregnancy on plasma cytokines and the febrile response to intraperitoneal administration of bacterial endotoxin in rats, Exp. Physiol., 88, 747, 10.1113/eph8802594

Fortier, 2004, Maternal exposure to bacterial endotoxin during pregnancy enhances amphetamine-induced locomotion and startle responses in adult rat offspring, J. Psychiatr. Res., 38, 335, 10.1016/j.jpsychires.2003.10.001

Fortier, 2004, The viral mimic, polyinosinic:polycytidylic acid, induces fever in rats via an interleukin-1-dependent mechanism, Am. J. Physiol., 287, R759

Fortier, 2007, Effects of prenatal infection on prepulse inhibition in the rat depend on the nature of the infectious agent and the stage of pregnancy, Behav. Brain Res., 181, 270, 10.1016/j.bbr.2007.04.016

Gayle, 2004, Maternal LPS induces cytokines in the amniotic fluid and corticotropin releasing hormone in the fetal rat brain, Am. J. Physiol., 286, R1024

Gilmore, 2005, Maternal poly I:C exposure during pregnancy regulates TNF alpha, BDNF, and NGF expression in neonatal brain and the maternal-fetal unit of the rat, J. Neuroimmunol., 159, 106, 10.1016/j.jneuroim.2004.10.008

Girard, 2009, Developmental motor deficits induced by combined fetal exposure to lipopolysaccharide and early neonatal hypoxia/ischemia: a novel animal model for cerebral palsy in very premature infants, Neuroscience, 158, 673, 10.1016/j.neuroscience.2008.10.032

Girard, 2010, IL-1 receptor antagonist protects against placental and neurodevelopmental defects induced by maternal inflammation, J. Immunol., 10.4049/jimmunol.0903349

Golan, 2005, Specific neurodevelopmental damage in mice offspring following maternal inflammation during pregnancy, Neuropharmacology, 48, 903, 10.1016/j.neuropharm.2004.12.023

Golan, 2006, Alterations in behavior in adult offspring mice following maternal inflammation during pregnancy, Dev. Psychobiol., 48, 162, 10.1002/dev.20116

Golan, 2006, Normal aging of offspring mice of mothers with induced inflammation during pregnancy, Neuroscience, 141, 1909, 10.1016/j.neuroscience.2006.05.045

Goto, 1994, LPS injected into the pregnant rat late in gestation does not induce fetal endotoxemia, Res. Commun. Mol. Pathol. Pharmacol., 85, 109

Guidotti, 2009, Characterization of the action of antipsychotic subtypes on valproate-induced chromatin remodeling, Trends Pharmacol. Sci., 30, 55, 10.1016/j.tips.2008.10.010

Haesaert, 1986, Transplacental effects of endotoxemia on fetal mouse brain, bone, and placental tissue, Pediatr. Pathol., 5, 167, 10.3109/15513818609041199

Haider, 2009, Human tumour necrosis factor: physiological and pathological roles in placenta and endometrium, Placenta, 30, 111, 10.1016/j.placenta.2008.10.012

Harnett, 2007, Dose-dependent lipopolysaccharide-induced fetal brain injury in the guinea pig, Am. J. Obstet. Gynecol., 197, 179.e1, 10.1016/j.ajog.2007.03.047

Kakinuma, 1997, Trophoblastic apoptosis in mice with preterm delivery and its suppression by urinary trypsin inhibitor, Obstet. Gynecol., 90, 117, 10.1016/S0029-7844(97)00176-2

Kapur, 2003, Half a century of antipsychotics and still a central role for dopamine D2 receptors, Prog. Neuropsychopharmacol. Biol. Psychiatry, 27, 1081, 10.1016/j.pnpbp.2003.09.004

Kimura-Takeuchi, 1992, The role of double-stranded RNA in induction of the acute-phase response in an abortive influenza virus infection model, J. Infect. Dis., 166, 1266, 10.1093/infdis/166.6.1266

Koga, 2009, Activation of TLR3 in the trophoblast is associated with preterm delivery, Am. J. Reprod. Immunol., 61, 196, 10.1111/j.1600-0897.2008.00682.x

Kumral, 2007, Erythropoietin attenuates lipopolysaccharide-induced white matter injury in the neonatal rat brain, Neonatology, 92, 269, 10.1159/000105493

Lanté, 2007, Neurodevelopmental damage after prenatal infection: role of oxidative stress in the fetal brain, Free Radic. Biol. Med., 42, 1231, 10.1016/j.freeradbiomed.2007.01.027

Lanté, 2008, Late N-acetylcysteine treatment prevents the deficits induced in the offspring of dams exposed to an immune stress during gestation, Hippocampus, 18, 602, 10.1002/hipo.20421

Larouche, 2005, Neuronal injuries induced by perinatal hypoxic–ischemic insults are potentiated by prenatal exposure to lipopolysaccharide: animal model for perinatally acquired encephalopathy, Dev. Neurosci., 27, 134, 10.1159/000085985

Li, 2009, Prenatal immune challenge is an environmental risk factor for brain and behavior change relevant to schizophrenia: evidence from MRI in a mouse model, PLoS One, 4, e6354, 10.1371/journal.pone.0006354

Libbey, 2005, Autistic disorder and viral infections, J. Neurovirol., 11, 1, 10.1080/13550280590900553

Lieberman, 2008, Antipsychotic drugs: comparison in animal models of efficacy, neurotransmitter regulation, and neuroprotection, Pharmacol. Rev., 60, 358, 10.1124/pr.107.00107

Limosin, 2003, Prenatal exposure to influenza as a risk factor for adult schizophrenia, Acta Psychiatr. Scand., 107, 331, 10.1034/j.1600-0447.2003.00052.x

Ling, 1998, Differentiation of mesencephalic progenitor cells into dopaminergic neurons by cytokines, Exp. Neurol., 149, 411, 10.1006/exnr.1998.6715

Ling, 2002, In utero bacterial endotoxin exposure causes loss of tyrosine hydroxylase neurons in the postnatal rat midbrain, Mov. Disord., 17, 116, 10.1002/mds.10078

Ling, 2004, Combined toxicity of prenatal bacterial endotoxin exposure and postnatal 6-hydroxydopamine in the adult rat midbrain, Neuroscience, 124, 619, 10.1016/j.neuroscience.2003.12.017

Ling, 2004, Rotenone potentiates dopamine neuron loss in animals exposed to lipopolysaccharide prenatally, Exp. Neurol., 190, 373, 10.1016/j.expneurol.2004.08.006

Ling, 2006, Progressive dopamine neuron loss following supra-nigral lipopolysaccharide (LPS) infusion into rats exposed to LPS prenatally, Exp. Neurol., 199, 499, 10.1016/j.expneurol.2006.01.010

Ling, 2009, Prenatal lipopolysaccharide does not accelerate progressive dopamine neuron loss in the rat as a result of normal aging, Exp. Neurol., 216, 312, 10.1016/j.expneurol.2008.12.004

Liu, 2004, Endotoxin exposure in utero increases ethanol consumption in adult male offspring, Neuroreport, 15, 203, 10.1097/00001756-200401190-00039

Liuzzi, 2005, Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response, Proc. Natl. Acad. Sci. USA, 102, 6843, 10.1073/pnas.0502257102

Liverman, 2006, Altered expression of pro-inflammatory and developmental genes in the fetal brain in a mouse model of maternal infection, Neurosci. Lett., 399, 220, 10.1016/j.neulet.2006.01.064

Lowe, 2008, Maternal infection and fever during late gestation are associated with altered synaptic transmission in the hippocampus of juvenile offspring rats, Am. J. Physiol., 295, R1563

Luheshi, 1998, Cytokines and fever. Mechanisms and sites of action, Ann. N. Y. Acad. Sci., 856, 83, 10.1111/j.1749-6632.1998.tb08316.x

Makinodan, 2008, Maternal immune activation in mice delays myelination and axonal development in the hippocampus of the offspring, J. Neurosci. Res., 86, 2190, 10.1002/jnr.21673

Marx, 2001, Cytokine effects on cortical neuron MAP-2 immunoreactivity: implications for schizophrenia, Biol. Psychiatry, 50, 743, 10.1016/S0006-3223(01)01209-4

McGrath, 2004, A systematic review of the incidence of schizophrenia: the distribution of rates and the influence of sex, urbanicity, migrant status and methodology, BMC Med., 2, 13, 10.1186/1741-7015-2-13

Mednick, 1988, Adult schizophrenia following prenatal exposure to an influenza epidemic, Arch. Gen. Psychiatry, 45, 189, 10.1001/archpsyc.1988.01800260109013

Mednick, 1994, Prenatal influenza infections and adult schizophrenia, Schizophr. Bull., 20, 263, 10.1093/schbul/20.2.263

Meyer, 2006, The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology, J. Neurosci., 26, 4752, 10.1523/JNEUROSCI.0099-06.2006

Meyer, 2006, Prenatal and postnatal maternal contributions in the infection model of schizophrenia, Exp. Brain Res., 173, 243, 10.1007/s00221-006-0419-5

Meyer, 2008, Preliminary evidence for a modulation of fetal dopaminergic development by maternal immune activation during pregnancy, Neuroscience, 154, 701, 10.1016/j.neuroscience.2008.04.031

Meyer, 2008, Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling, Mol. Psychiatry, 13, 208, 10.1038/sj.mp.4002042

Meyer, 2008, Adult brain and behavioral pathological markers of prenatal immune challenge during early/middle and late fetal development in mice, Brain Behav. Immun., 22, 469, 10.1016/j.bbi.2007.09.012

Meyer, 2008, Evaluating early preventive antipsychotic and antidepressant drug treatment in an infection-based neurodevelopmental mouse model of schizophrenia, Schizophr. Bull.

Meyer, 2008, Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after in utero immune challenge, Neuropsychopharmacology, 33, 441, 10.1038/sj.npp.1301413

Meyer, 2009, In-vivo rodent models for the experimental investigation of prenatal immune activation effects in neurodevelopmental brain disorders, Neurosci. Biobehav. Rev., 33, 1061, 10.1016/j.neubiorev.2009.05.001

Mortensen, 2007, Early infections of Toxoplasma gondii and the later development of schizophrenia, Schizophr. Bull., 33, 741, 10.1093/schbul/sbm009

Mouihate, 2008, Suppression of the febrile response in late gestation: evidence, mechanisms and outcomes, J. Neuroendocrinol., 20, 508, 10.1111/j.1365-2826.2008.01666.x

Munk-Jorgensen, 2001, Epidemiology in neurobiological research: exemplified by the influenza–schizophrenia theory, Br. J. Psychiatry Suppl., 40, s30, 10.1192/bjp.178.40.s30

Murphy, 1995, Case-control study of antenatal and intrapartum risk factors for cerebral palsy in very preterm singleton babies, Lancet, 346, 1449, 10.1016/S0140-6736(95)92471-X

Nilsson, 2001, Maternal endotoxemia results in obesity and insulin resistance in adult male offspring, Endocrinology, 142, 2622, 10.1210/endo.142.6.8191

Ning, 2008, Maternally-administered lipopolysaccharide (LPS) increases tumor necrosis factor alpha in fetal liver and fetal brain: its suppression by low-dose LPS pretreatment, Toxicol. Lett., 176, 13, 10.1016/j.toxlet.2007.08.002

Niwa, 2010, Knockdown of DISC1 by in utero gene transfer disturbs postnatal dopaminergic maturation in the frontal cortex and leads to adult behavioral deficits, Neuron, 65, 480, 10.1016/j.neuron.2010.01.019

Nyffeler, 2006, Maternal immune activation during pregnancy increases limbic GABAA receptor immunoreactivity in the adult offspring: implications for schizophrenia, Neuroscience, 143, 51, 10.1016/j.neuroscience.2006.07.029

O’Callaghan, 1991, Schizophrenia after prenatal exposure to 1957 A2 influenza epidemic, Lancet, 337, 1248, 10.1016/0140-6736(91)92919-S

O’Callaghan, 1994, The relationship of schizophrenic births to 16 infectious diseases, Br. J. Psychiatry, 165, 353, 10.1192/bjp.165.3.353

Offenbacher, 2005, Effects of maternal Campylobacter rectus infection on murine placenta, fetal and neonatal survival, and brain development, J. Periodontol., 76, 2133, 10.1902/jop.2005.76.11-S.2133

Opal, 2007, The host response to endotoxin, antilipopolysaccharide strategies, and the management of severe sepsis, Int. J. Med. Microbiol., 297, 365, 10.1016/j.ijmm.2007.03.006

Ozawa, 2006, Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring: a neurodevelopmental animal model of schizophrenia, Biol. Psychiatry, 59, 546, 10.1016/j.biopsych.2005.07.031

Paintlia, 2004, N-Acetylcysteine prevents endotoxin-induced degeneration of oligodendrocyte progenitors and hypomyelination in developing rat brain, J. Neurosci. Res., 78, 347, 10.1002/jnr.20261

Paintlia, 2008, Lipopolysaccharide-induced peroxisomal dysfunction exacerbates cerebral white matter injury: attenuation by N-acetyl cysteine, Exp. Neurol., 210, 560, 10.1016/j.expneurol.2007.12.011

Qui, 1998, Chronic interleukin-6 alters NMDA receptor-mediated membrane responses and enhances neurotoxicity in developing CNS neurons, J. Neurosci., 18, 10445, 10.1523/JNEUROSCI.18-24-10445.1998

Ray, 1991, Variability in LPS composition, antigenicity and reactogenicity of phase variants of Bordetella pertussis, FEMS Microbiol. Lett., 63, 211, 10.1111/j.1574-6968.1991.tb04531.x

Reisenberger, 1996, The transfer of interleukin-8 across the human placenta perfused in vitro, Obstet. Gynecol., 87, 613, 10.1016/0029-7844(95)00473-4

Reul, 1994, Prenatal immune challenge alters the hypothalamic–pituitary–adrenocortical axis in adult rats, J. Clin. Invest., 93, 2600, 10.1172/JCI117272

Romanovsky, 1998, Fever and hypothermia: two adaptive thermoregulatory responses to systemic inflammation, Med. Hypotheses, 50, 219, 10.1016/S0306-9877(98)90022-6

Romero, 1987, Failure of endotoxin to cross the chorioamniotic membranes in vitro, Am. J. Perinatol., 4, 360, 10.1055/s-2007-999808

Romero, 2007, Neurobehavioral and immunological consequences of prenatal immune activation in rats. Influence of antipsychotics, Neuropsychopharmacology, 32, 1791, 10.1038/sj.npp.1301292

Romero, 2010, Ontogeny of sensorimotor gating and immune impairment induced by prenatal immune challenge in rats: implications for the etiopathology of schizophrenia, Mol. Psychiatry, 15, 372, 10.1038/mp.2008.44

Romijn, 1991, At what age is the developing cerebral cortex of the rat comparable to that of the full-term newborn human baby?, Early Hum. Dev., 26, 61, 10.1016/0378-3782(91)90044-4

Roth, 2009, Molecular aspects of fever and hyperthermia, Immunol. Allergy Clin. North Am., 29, 229, 10.1016/j.iac.2009.02.005

Roumier, 2008, Prenatal activation of microglia induces delayed impairment of glutamatergic synaptic function, PLoS One, 3, e2595, 10.1371/journal.pone.0002595

Rousset, 2006, Maternal exposure to LPS induces hypomyelination in the internal capsule and programmed cell death in the deep gray matter in newborn rats, Pediatr. Res., 59, 428, 10.1203/01.pdr.0000199905.08848.55

Rousset, 2008, Antenatal bacterial endotoxin sensitizes the immature rat brain to postnatal excitotoxic injury, J. Neuropathol. Exp. Neurol., 67, 994, 10.1097/NEN.0b013e31818894a1

Samuelsson, 2006, Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in hippocampus with NMDA/GABA(A) dysregulation and impaired spatial learning, Am. J. Physiol., 290, R1345

Selten, 2009, Schizophrenia and 1957 Pandemic of Influenza: meta-analysis, Schizophr. Bull.

Sham, 1992, Schizophrenia following pre-natal exposure to influenza epidemics between 1939 and 1960, Br. J. Psychiatry, 160, 461, 10.1192/bjp.160.4.461

Shi, 2003, Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring, J. Neurosci., 23, 297, 10.1523/JNEUROSCI.23-01-00297.2003

Shi, 2005, Maternal influenza infection is likely to alter fetal brain development indirectly: the virus is not detected in the fetus, Int. J. Dev. Neurosci., 23, 299, 10.1016/j.ijdevneu.2004.05.005

Shi, 2009, Activation of the maternal immune system alters cerebellar development in the offspring, Brain Behav. Immun., 23, 116, 10.1016/j.bbi.2008.07.012

Smith, 2007, Maternal immune activation alters fetal brain development through interleukin-6, J. Neurosci., 27, 10695, 10.1523/JNEUROSCI.2178-07.2007

Snyder-Keller, 2008, Prenatal inflammatory effects on nigrostriatal development in organotypic cultures, Brain Res., 1233, 160, 10.1016/j.brainres.2008.07.106

Song, 1999, Variations of nucleus accumbens dopamine and serotonin following systemic interleukin-1, interleukin-2 or interleukin-6 treatment, Neuroscience, 88, 823, 10.1016/S0306-4522(98)00271-1

Sørensen, 2009, Association between prenatal exposure to bacterial infection and risk of schizophrenia, Schizophr. Bull., 35, 631, 10.1093/schbul/sbn121

Soszynski, 1991, Course of fever response to repeated administration of sublethal doses of lipopolysaccharides, polyinosinic:polycytidylic acid and muramyl dipeptide to rabbits, Experientia, 47, 43, 10.1007/BF02041248

Spencer, 2008, Central and peripheral neuroimmune responses: hyporesponsiveness during pregnancy, J. Physiol., 586, 399, 10.1113/jphysiol.2007.144006

Suvisaari, 1999, Association between prenatal exposure to poliovirus infection and adult schizophrenia, Am. J. Psychiatry, 156, 1100, 10.1176/ajp.156.7.1100

Suzuki, 2008, The course of fever following influenza virus infection in children treated with oseltamivir, J. Med. Virol., 80, 1065, 10.1002/jmv.21144

Suzuki, 2007, Natural course of fever during influenza virus infection in children, Clin. Pediatr. (Phila.), 46, 76, 10.1177/0009922806289588

Swerdlow, 2001, Neural circuit regulation of prepulse inhibition of startle in the rat: current knowledge and future challenges, Psychopharmacology, 156, 194, 10.1007/s002130100799

Takei, 1996, Relationship between in utero exposure to influenza epidemics and risk of schizophrenia in Denmark, Biol. Psychiatry, 40, 817, 10.1016/0006-3223(95)00592-7

Torrey, 1988, Schizophrenic births and viral diseases in two states, Schizophr. Res., 1, 73, 10.1016/0920-9964(88)90043-6

Urakubo, 2001, Prenatal exposure to maternal infection alters cytokine expression in the placenta, amniotic fluid, and fetal brain, Schizophr. Res., 47, 27, 10.1016/S0920-9964(00)00032-3

von Coelln, 1995, Screening of interleukins for survival-promoting effects on cultured mesencephalic dopaminergic neurons from embryonic rat brain, Dev. Brain Res., 89, 150, 10.1016/0165-3806(95)00123-U

Wang, 2009, Dopaminergic and serotoninergic deficiencies in young adult rats prenatally exposed to the bacterial lipopolysaccharide, Brain Res., 126, 196, 10.1016/j.brainres.2009.02.022

Wang, 2010, Age- and gender-dependent impairments of neurobehaviors in mice whose mothers were exposed to lipopolysaccharide during pregnancy, Toxicol. Lett., 192, 245, 10.1016/j.toxlet.2009.10.030

Weaver, 2004, Epigenetic programming by maternal behavior, Nat. Neurosci., 7, 847, 10.1038/nn1276

Wijkstra, 1991, Endotoxin treatment of pregnant rats affects sexual behavior of the male offspring, Physiol. Behav., 49, 647, 10.1016/0031-9384(91)90294-X

Wilkerson, 2002, Perinatal complications as predictors of infantile autism, Int. J. Neurosci., 112, 1085, 10.1080/00207450290026076

Wilkinson, 1990, Centrally acting vasopressin contributes to endotoxin tolerance, Am. J. Physiol., 258, R443

Winter, 2008, Prenatal immune activation leads to multiple changes in basal neurotransmitter levels in the adult brain: implications for brain disorders of neurodevelopmental origin such as schizophrenia, Int. J. Neuropsychopharmacol., 12, 513, 10.1017/S1461145708009206

Winter, 2008, Dopamine and serotonin levels following prenatal viral infection in mouse – implications for psychiatric disorders such as schizophrenia and autism, Eur. Neuropsychopharmacol., 18, 712, 10.1016/j.euroneuro.2008.06.001

Wolff, 2008, Immune activation during mid-gestation disrupts sensorimotor gating in rat offspring, Behav. Brain Res., 190, 156, 10.1016/j.bbr.2008.02.021

Woolf, 2007, Transplacental murine cytomegalovirus infection in the brain of SCID mice, Virol. J., 4, 26, 10.1186/1743-422X-4-26

Wu, 2002, Systematic review of chorioamnionitis and cerebral palsy, Ment. Retard. Dev. Disabil. Res. Rev., 8, 25, 10.1002/mrdd.10003

Wu, 2000, Chorioamnionitis as a risk factor for cerebral palsy: a meta-analysis, JAMA, 284, 1417, 10.1001/jama.284.11.1417

Xiao, 2009, Serological pattern consistent with infection with type I Toxoplasma gondii in mothers and risk of psychosis among adult offspring, Microbes Infect., 11, 1011, 10.1016/j.micinf.2009.07.007

Xu, 2006, Tumor necrosis factor alpha partially contributes to lipopolysaccharide-induced intra-uterine fetal growth restriction and skeletal development retardation in mice, Toxicol. Lett., 163, 20, 10.1016/j.toxlet.2005.09.009

Yesilirmak, 2007, Activated protein C reduces endotoxin-induced white matter injury in the developing rat brain, Brain Res., 1164, 14, 10.1016/j.brainres.2007.04.083

Zahn-Waxler, 2008, Disorders of childhood and adolescence: gender and psychopathology, Annu. Rev. Clin. Psychol., 4, 275, 10.1146/annurev.clinpsy.3.022806.091358

Zalcman, 1994, Cytokine-specific central monoamine alterations induced by interleukin-1, -2 and -6, Brain Res., 643, 40, 10.1016/0006-8993(94)90006-X

Zalcman, 1999, Interleukin-6 increases sensitivity to the locomotor-stimulating effects of amphetamine in rats, Brain Res., 847, 276, 10.1016/S0006-8993(99)02063-6

Zammit, 2009, Investigating whether adverse prenatal and perinatal events are associated with non-clinical psychotic symptoms at age 12years in the ALSPAC birth cohort, Psychol. Med., 39, 1457, 10.1017/S0033291708005126

Zaretsky, 2004, Transfer of inflammatory cytokines across the placenta, Obstet. Gynecol., 103, 546, 10.1097/01.AOG.0000114980.40445.83

Zhang, 2010, Epigenetics and the environmental regulation of the genome and its function, Annu. Rev. Psychol., 61, 439, 10.1146/annurev.psych.60.110707.163625

Zhang, 2007, Lipopolysaccharide (LPS) up-regulates the expression of haem oxygenase-1 in mouse placenta, Placenta, 28, 951, 10.1016/j.placenta.2007.04.003

Zhu, 2007, Altered glutathione homeostasis in animals prenatally exposed to lipopolysaccharide, Neurochem. Int., 50, 671, 10.1016/j.neuint.2006.12.013

Zuckerman, 2003, Post-pubertal emergence of disrupted latent inhibition following prenatal immune activation, Psychopharmacology, 169, 308, 10.1007/s00213-003-1461-7

Zuckerman, 2005, Maternal immune activation leads to behavioral and pharmacological changes in the adult offspring, J. Psychiatr. Res., 39, 311, 10.1016/j.jpsychires.2004.08.008

Zuckerman, 2003, Immune activation during pregnancy in rats leads to a postpubertal emergence of disrupted latent inhibition, dopaminergic hyperfunction, and altered limbic morphology in the offspring: a novel neurodevelopmental model of schizophrenia, Neuropsychopharmacology, 28, 1778, 10.1038/sj.npp.1300248