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Alteration of Neurodevelopment and behavior by Maternal Immune Activation

  • Chapter
The Neuroimmunological Basis of Behavior and Mental Disorders

Abstract

The immune system rapidly responds to pathogens by releasing a variety of signaling molecules that trigger a number of infection-fighting cellular programs. These same signaling pathways (e.g., NF-nκB, JAX/STAT, ERK) are used by the developing brain to orchestrate programs of cell proliferation, differentiation, and migration. Thus, when a pregnant woman falls ill, there is the potential for crosstalk between the maternal immune response and the developing fetal brain. In fact, maternal infections are significant environmental risk factors for schizophrenia and autism. There are several animal models in which infection-induced maternal immune activation causes behavioral, histological, and gene expression changes in the offspring that are reminiscent of human mental disorders. We review both human and animal data that demonstrate these effects of maternal immune activation, and discuss potential mechanisms through which the maternal immune system may alter brain development.

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References

  • Akshoomoff N, Lord C, Lincoln AJ, Courchesne RY, Carper RA, Townsend J, Courchesne E (2004) Outcome classification of preschool children with autism spectrum disorders using MRI brain measures. J Am Acad Child Adolesc Psychiatry 43:349–357.

    Article  PubMed  Google Scholar 

  • Arion D, Unger T, Lewis DA, Levitt P, Mirnics K (2007) Molecular evidence for increased expression of genes related to immune and chaperone function in the prefrontal cortex in schizophrenia. Biol Psychiatry 62:711–721.

    Article  PubMed  CAS  Google Scholar 

  • Ashdown H, Dumont Y, Ng M, Poole S, Boksa P, Luheshi GN (2006) The role of cytokines in mediating effects of prenatal infection on the fetus: implications for schizophrenia. Mol Psychiatry 11:47–55.

    Article  PubMed  CAS  Google Scholar 

  • Babulas V, Factor-Litvak P, Goetz R, Schaefer CA, Brown AS (2006) Prenatal exposure to maternal genital and reproductive infections and adult schizophrenia. Am J Psychiatry 163:927–929.

    Article  PubMed  Google Scholar 

  • Bagalkote H, Pang D, Jones P (2001) Maternal influenza and schizophrenia in the offspring. Intl J Ment Health 39:3–21.

    Google Scholar 

  • Bakos J, Duncko R, Makatsori A, Pirnik Z, Kiss A, Jezova D (2004) Prenatal immune challenge affects growth, behavior, and brain dopamine in offspring. Ann N Y Acad Sci 1018:281–287.

    Article  PubMed  CAS  Google Scholar 

  • Balschun D, Wetzel W, Del Rey A, Pitossi F, Schneider H, Zuschratter W, Besedovsky HO (2004) Interleukin-6: a cytokine to forget. Faseb J 18:1788–1790.

    PubMed  CAS  Google Scholar 

  • Barbazanges A, Piazza PV, Le Moal M, Maccari S (1996) Maternal glucocorticoid secretion mediates long-term effects of prenatal stress. J Neurosci 16:3943–3949.

    Google Scholar 

  • Bauer S, Kerr BJ, Patterson PH (2007) The neuropoietic cytokine family in development, plasticity, disease and injury. Nat Rev Neurosci 8:221–232.

    Article  PubMed  CAS  Google Scholar 

  • Bell MJ, Hallenbeck JM, Gallo V (2004) Determining the fetal inflammatory response in an experimental model of intrauterine inflammation in rats. Pediatr Res 56:541–546.

    Article  PubMed  CAS  Google Scholar 

  • Beloosesky R, Gayle DA, Amidi F, Nunez SE, Babu J, Desai M, Ross MG (2006) N-acetyl-cysteine suppresses amniotic fluid and placenta inflammatory cytokine responses to lipopolysaccharide in rats. Am J Obstet Gynecol 194:268–273.

    Article  PubMed  CAS  Google Scholar 

  • Bilbo SD, Biedenkapp JC, Der-Avakian A, Watkins LR, Rudy JW, Maier SF (2005a) Neonatal infection-induced memory impairment after lipopolysaccharide in adulthood is prevented via caspase-1 inhibition. J Neurosci 25:8000–8009.

    Article  CAS  Google Scholar 

  • Bilbo SD, Levkoff LH, Mahoney JH, Watkins LR, Rudy JW, Maier SF (2005b) Neonatal infection induces memory impairments following an immune challenge in adulthood. Behav Neurosci 119:293–301.

    Article  CAS  Google Scholar 

  • Bobetsis YA, Barros SP, Offenbacher S (2006) Exploring the relationship between periodontal disease and pregnancy complications. J Am Dental Assoc 137:7s–13s.

    Google Scholar 

  • Boisse L, Mouihate A, Ellis S, Pittman QJ (2004) Long-term alterations in neuroimmune responses after neonatal exposure to lipopolysaccharide. J Neurosci 24:4928–4934.

    Article  PubMed  CAS  Google Scholar 

  • Boris M, Kaiser CC, Goldblatt A, Elice MW, Edelson SM, Adams JB, Feinstein DL (2007) Effect of pioglitazone treatment on behavioral symptoms in autistic children. J Neuroinflammation 4:3.

    Article  PubMed  Google Scholar 

  • Borrell J, Vela JM, Arevalo-Martin A, Molina-Holgado E, Guaza C (2002) Prenatal immune challenge disrupts sensorimotor gating in adult rats. Implications for the etiopathogenesis of schizophrenia. Neuropsychopharmacology 26:204–215.

    CAS  Google Scholar 

  • Brown AS, Begg MD, Gravenstein S, Schaefer CA, Wyatt RJ, Bresnahan M, Babulas VP, Susser ES (2004a) Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry 61:774–780.

    Article  Google Scholar 

  • Brown AS, Hooton J, Schaefer CA, Zhang H, Petkova E, Babulas V, Perrin M, Gorman JM, Susser ES (2004b) Elevated maternal interleukin-8 levels and risk of schizophrenia in adult offspring. Am J Psychiatry 161:889–895.

    Article  Google Scholar 

  • Brown AS, Schaefer CA, Quesenberry CP, Jr., Liu L, Babulas VP, Susser ES (2005) Maternal exposure to toxoplasmosis and risk of schizophrenia in adult offspring. Am J Psychiatry 162:767–773.

    Article  PubMed  Google Scholar 

  • Cai Z, Pan ZL, Pang Y, Evans OB, Rhodes PG (2000) Cytokine induction in fetal rat brains and brain injury in neonatal rats after maternal lipopolysaccharide administration. Pediatr Res 47:64–72.

    Article  PubMed  CAS  Google Scholar 

  • Capuron L, Dantzer R (2003) Cytokines and depression: the need for a new paradigm. Brain Behav Immun 17 Suppl 1:S119–124.

    Article  Google Scholar 

  • Chess S (1977) Follow-up report on autism in congenital rubella. J Autism Child Schizophr 7:69–81.

    Article  PubMed  CAS  Google Scholar 

  • Chez MG, Dowling T, Patel PB, Khanna P, Kominsky M (2007) Elevation of tumor necrosis factor-alpha in cerebrospinal fluid of autistic children. Pediatr Neurol 36:361–365.

    Article  PubMed  Google Scholar 

  • Ciaranello AL, Ciaranello RD (1995) The neurobiology of infantile autism. Annu Rev Neurosci 18:101–128.

    Article  PubMed  CAS  Google Scholar 

  • Clancy B, Darlington RB, Finlay BL (2001) Translating developmental time across mammalian species. Neuroscience 105:7–17.

    Article  PubMed  CAS  Google Scholar 

  • Crawley JN (2007) Mouse behavioral assays relevant to the symptoms of autism. Brain Pathol 17:448–459.

    Article  PubMed  Google Scholar 

  • Croonenberghs J, Bosmans E, Deboutte D, Kenis G, Maes M (2002) Activation of the inflammatory response system in autism. Neuropsychobiology 45:1–6.

    Article  PubMed  CAS  Google Scholar 

  • Curran LK, Newschaffer CJ, Lee LC, Crawford SO, Johnston MV, Zimmerman AW (2007) Behaviors associated with fever in children with autism spectrum disorders. Pediatrics 120:e1386–1392.

    Article  PubMed  Google Scholar 

  • 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 

  • Dammann O, Kuban KC, Leviton A (2002) Perinatal infection, fetal inflammatory response, white matter damage, and cognitive limitations in children born preterm. Ment Retard Dev Disabil Res Rev 8:46–50.

    Article  PubMed  Google Scholar 

  • Davis JO, Phelps JA, Bracha HS (1995) Prenatal development of monozygotic twins and concordance for schizophrenia. Schizophr Bull 21:357–366.

    PubMed  CAS  Google Scholar 

  • Desmond MM, Wilson GS, Melnick JL, Singer DB, Zion TE, Rudolph AJ, Pineda RG, Ziai MH, Blattner RJ (1967) Congenital rubella encephalitis. Course and early sequelae. J Pediatr 71:311–331.

    CAS  Google Scholar 

  • Elovitz MA, Mrinalini C, Sammel MD (2006) Elucidating the early signal transduction pathways leading to fetal brain injury in preterm birth. Pediatr Res 59:50–55.

    Article  PubMed  Google Scholar 

  • Fatemi SH, Sidwell R, Kist D, Akhter P, Meltzer HY, Bailey K, Thuras P, Sedgwick J (1998) Differential expression of synaptosome-associated protein 25 kDa [SNAP-25] in hippocampi of neonatal mice following exposure to human influenza virus in utero. Brain Res 800:1–9.

    Article  PubMed  CAS  Google Scholar 

  • Fatemi SH, Emamian ES, Kist D, Sidwell RW, Nakajima K, Akhter P, Shier A, Sheikh S, Bailey K (1999) Defective corticogenesis and reduction in Reelin immunoreactivity in cortex and hippocampus of prenatally infected neonatal mice. Mol Psychiatry 4:145–154.

    Article  PubMed  CAS  Google Scholar 

  • Fatemi SH, Earle J, Kanodia R, Kist D, Emamian ES, Patterson PH, Shi L, Sidwell R (2002) Prenatal viral infection leads to pyramidal cell atrophy and macrocephaly in adulthood: implications for genesis of autism and schizophrenia. Cell Mol Neurobiol 22:25–33.

    Article  PubMed  Google Scholar 

  • Fortier ME, Joober R, Luheshi GN, Boksa P (2004) Maternal exposure to bacterial endotoxin during pregnancy enhances amphetamine-induced locomotion and startle responses in adult rat offspring. J Psychiatr Res 38:335–345.

    Article  PubMed  Google Scholar 

  • Francis D, Diorio J, Liu D, Meaney MJ (1999) Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286:1155–1158.

    Article  PubMed  CAS  Google Scholar 

  • Garbett K, Ebert P, Lintas C, Mirnics K, Persico A (2007) Immune transcript disturbances in temporal cortex of autistic brains. 2007 Society for Neuroscience poster presentation.

    Google Scholar 

  • Garver DL, Tamas RL, Holcomb JA (2003) Elevated interleukin-6 in the cerebrospinal fluid of a previously delineated schizophrenia subtype. Neuropsychopharmacology 28:1515–1520.

    Article  PubMed  CAS  Google Scholar 

  • Gilmore JH, Jarskog LF, Vadlamudi S, Lauder J (2004) Prenatal infection and risk for schizophrenia:IL-I beta, IL-6, and TNF alpha inhibit cortical neuron dendrite development. Neuropsychopharmacology 29:1221–1229.

    Article  CAS  Google Scholar 

  • Gilmore JH, Jarskog LF, Vadlamudi S (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 159:106–112.

    Article  PubMed  CAS  Google Scholar 

  • Golan HM, Lev V, Hallak M, Sorokin Y, Huleihel M (2005) Specific neurodevelopmental damage in mice offspring following maternal inflammation during pregnancy. Neuropharmacology 48:903–917.

    Article  PubMed  CAS  Google Scholar 

  • Golan H, Stilman M, Lev V, Huleihel M (2006) Normal aging of offspring mice of mothers with induced inflammation during pregnancy. Neuroscience 141:1909–1918.

    Article  PubMed  CAS  Google Scholar 

  • Han YW, Redline RW, Li M, Yin L, Hill GB, McCormick TS (2004) Fusobacterium nucleatum induces premature and term stillbirths in pregnant mice: implication of oral bacteria in preterm birth. Infect Immun 72:2272–2279.

    Article  PubMed  CAS  Google Scholar 

  • Hava G, Vered L, Yael M, Mordechai H, Mahoud H (2006) Alterations in behavior in adult offspring mice following maternal inflammation during pregnancy. Dev Psychobiol 48:162–168.

    Article  PubMed  Google Scholar 

  • Hodyl NA, Krivanek KM, Lawrence E, Clifton VL, Hodgson DM (2007) Prenatal exposure to a pro-inflammatory stimulus causes delays in the development of the innate immune response to LPS in the offspring. J Neuroimmunol 190:61–71.

    Article  PubMed  CAS  Google Scholar 

  • Hyman SL, Arndt TL, Rodier PM (2005) Environmental Agents and Autism: Once and Future Associations. Int Rev Res Ment Ret 30:171–194.

    Article  Google Scholar 

  • Jankowsky JL, Patterson PH (1999) Cytokine and growth factor involvement in long-term potentiation.

    Google Scholar 

  • Mol Cell Neurosci 14:273–286.

    Google Scholar 

  • Lasala N, Zhou H (2007) Effects of maternal exposure to LPS on the inflammatory response in the offspring. J Neuroimmunol 189:95–101.

    Article  PubMed  CAS  Google Scholar 

  • Lemery-Chalfant K, Goldsmith HH, Schmidt NL, Arneson CL, Van Hulle CA (2006) Wisconsin Twin Panel: current directions and findings. Twin Res Hum Genet 9:1030–1037.

    Article  PubMed  Google Scholar 

  • Levitt NS, Lindsay RS, Holmes MC, Seckl JR (1996) Dexamethasone in the last week of pregnancy attenuates hippocampal glucocorticoid receptor gene expression and elevates blood pressure in the adult offspring in the rat. Neuroendocrinology 64:412–418.

    Article  PubMed  CAS  Google Scholar 

  • Libbey JE, Sweeten TL, McMahon WM, Fujinami RS (2005) Autistic disorder and viral infections. J Neurovirol 11:1–10.

    Article  PubMed  Google Scholar 

  • Lin D, Smith MA, Champagne C, Elter J, Beck J, Offenbacher S (2003a) Porphyromonas gingivalis infection during pregnancy increases maternal tumor necrosis factor alpha, suppresses maternal interleukin-10, and enhances fetal growth restriction and resorption in mice. Infect Immun 71:5156–5162.

    Article  CAS  Google Scholar 

  • Lin D, Smith MA, Elter J, Champagne C, Downey CL, Beck J, Offenbacher S (2003b) Porphyromonas gingivalis infection in pregnant mice is associated with placental dissemination, an increase in the placental Th1/Th2 cytokine ratio, and fetal growth restriction. Infect Immun 71:5163–5168.

    Article  CAS  Google Scholar 

  • Ling Z, Chang QA, Tong CW, Leurgans SE, Lipton JW, Carvey PM (2004) Rotenone potentiates dopamine neuron loss in animals exposed to lipopolysaccharide prenatally. Exp Neurol 190:373–383.

    Article  PubMed  CAS  Google Scholar 

  • Liverman CS, Kaftan HA, Cui L, Hersperger SG, Taboada E, Klein RM, Berman NE (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 

  • Mankoski RE, Collins M, Ndosi NK, Mgalla EH, Sarwatt VV, Folstein SE (2006) Etiologies of autism in a case-series from Tanzania. J Autism Dev Disord 36:1039–1051.

    Article  PubMed  Google Scholar 

  • Mednick SA, Machon RA, Huttunen MO, Bonett D (1988) Adult schizophrenia following prenatal exposure to an influenza epidemic. Arch Gen Psychiatry 45:189–192.

    PubMed  CAS  Google Scholar 

  • Meyer U, Feldon J, Schedlowski M, Yee BK (2006a) Immunological stress at the maternal-foetal interface: a link between neurodevelopment and adult psychopathology. Brain Behav Immun 20:378–388.

    Article  CAS  Google Scholar 

  • Meyer U, Nyffeler M, Engler A, Urwyler A, Schedlowski M, Knuesel I, Yee BK, Feldon J (2006b) The time of prenatal immune challenge determines the specificity of inflammation-mediated brain and behavioral pathology. J Neurosci 26:4752–4762.

    Article  CAS  Google Scholar 

  • Meyer U, Murray PJ, Urwyler A, Yee BK, Schedlowski M, Feldon J (2008) Adult behavioral and pharmacological dysfunctions following disruption of the fetal brain balance between pro-inflammatory and IL-10-mediated anti-inflammatory signaling. Mol Psychiatr 13(2):208–221.

    Article  CAS  Google Scholar 

  • Morgan JT, Chana G, Buckwalter J, Courchesne E, Everall IP (2007) Increased Iba-1 positive microglial cell denisty in the autistic brain. 2007 Society for Neuroscience poster presentation.

    Google Scholar 

  • Nawa H, Takei N (2006) Recent progress in animal modeling of immune inflammatory processes in schizophrenia: implication of specific cytokines. Neurosci Res 56:2–13.

    Article  PubMed  CAS  Google Scholar 

  • Nyffeler M, Meyer U, Yee BK, Feldon J, Knuesel I (2006) Maternal immune activation during pregnancy increases limbic GABAA receptor immunoreactivity in the adult offspring: implications for schizophrenia. Neuroscience 143:51–62.

    Article  PubMed  CAS  Google Scholar 

  • O’Callaghan E, Sham PC, Takei N, Murray G, Glover G, Hare EH, Murray RM (1994) The relationship of schizophrenic births to 16 infectious diseases. Br J Psychiatry 165:353–356.

    Article  PubMed  CAS  Google Scholar 

  • Ozawa K, Hashimoto K, Kishimoto T, Shimizu E, Ishikura H, Iyo M (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 59:546–554.

    Article  PubMed  CAS  Google Scholar 

  • Paintlia MK, Paintlia AS, Barbosa E, Singh I, Singh AK (2004) N-acetylcysteine prevents endotoxin- induced degeneration of oligodendrocyte progenitors and hypomyelination in developing rat brain. J Neurosci Res 78:347–361.

    Article  PubMed  CAS  Google Scholar 

  • Palmen SJ, van Engeland H, Hof PR, Schmitz C (2004) Neuropathological findings in autism. Brain 127:2572–2583.

    Article  PubMed  Google Scholar 

  • Patterson PH (2002) Maternal infection: window on neuroimmune interactions in fetal brain development and mental illness. Curr Opin Neurobiol 12:115–118.

    Article  PubMed  CAS  Google Scholar 

  • Patterson PH (2005) Maternal influenza infection leads to neuropathology and behavioral abnormalities in adult offspring. Neuropsychopharmacology 30:S9–S9.

    Article  Google Scholar 

  • Paul R, Koedel U, Winkler F, Kieseier BC, Fontana A, Kopf M, Hartung HP, Pfister HW (2003) Lack of IL-6 augments inflammatory response but decreases vascular permeability in bacterial meningitis. Brain 126:1873–1882.

    Article  PubMed  Google Scholar 

  • Perry W, Minassian A, Lopez B, Maron L, Lincoln A (2007) Sensorimotor Gating Deficits in Adults with Autism. Biol Psychiatry 61(4):482–486.

    Article  PubMed  Google Scholar 

  • Phelps JA, Davis JO, Schartz KM (1997) Nature, Nurture, and Twin Research Strategies. Curr Dir Psychol Sci 6:117–121.

    Article  Google Scholar 

  • Pierce K, Courchesne E (2001) Evidence for a cerebellar role in reduced exploration and stereotyped behavior in autism. Biol Psychiatry 49:655–664.

    Article  PubMed  CAS  Google Scholar 

  • Piontkewitz Y, Weiner I, Assaf Y (2007) Post-pubertal emergence of schizophrenia-like abnormalaties following prenatal immune system activation and thier prevention: Modeling the disorder and its prodrome. In: 7th IBRO World Congress of Neuroscience, p 45. Melbourne, Australia.

    Google Scholar 

  • Ponzio NM, Servatius R, Beck K, Marzouk A, Kreider T (2007) Cytokine levels during pregnancy influence immunological profiles and neurobehavioral patterns of the offspring. Ann N Y Acad Sci 1107:118–128.

    Article  PubMed  CAS  Google Scholar 

  • Relier JP (2001) Influence of maternal stress on fetal behavior and brain development. Biol Neonate 79:168–171.

    Google Scholar 

  • Robertson SA, Skinner RJ, Care AS (2006) Essential role for IL-10 in resistance to lipopolysaccharide- induced preterm labor in mice. J Immunol 177:4888–4896.

    PubMed  CAS  Google Scholar 

  • Romero E, Ali C, Molina-Holgado E, Castellano B, Guaza C, Borrell J (2007) Neurobehavioral and immunological consequences of prenatal immune activation in rats. Influence of antipsychotics. Neuropsychopharmacology 32:1791–1804.

    Article  PubMed  CAS  Google Scholar 

  • Saetre P, Emilsson L, Axelsson E, Kreuger J, Lindholm E, Jazin E (2007) Inflammation-related genes up-regulated in schizophrenia brains. BMC Psychiatry 7:46.

    Article  PubMed  Google Scholar 

  • Saliba E, Henrot A (2001) Inflammatory mediators and neonatal brain damage. Biol Neonate 79:224–227.

    Article  PubMed  CAS  Google Scholar 

  • Samuelsson AM, Jennische E, Hansson HA, Holmang A (2006) Prenatal exposure to interleukin-6 results in inflammatory neurodegeneration in hippocampus with NMDA/GABA(A) dysregulation and impaired spatial learning. Am J Physiol Regul Integr Comp Physiol 290:R1345–1356.

    PubMed  CAS  Google Scholar 

  • Sargent IL, Borzychowski AM, Redman CW (2006) NK cells and human pregnancy – an inflammatory view. Trends Immunol 27:399–404.

    Article  PubMed  CAS  Google Scholar 

  • Schiepers OJ, Wichers MC, Maes M (2005) Cytokines and major depression. Prog Neuropsychopharmacol Biol Psychiatry 29:201–217.

    Article  PubMed  CAS  Google Scholar 

  • Shi L, Fatemi SH, Sidwell RW, Patterson PH (2003) Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J Neurosci 23:297–302.

    PubMed  Google Scholar 

  • Shi L, Tu N, Patterson PH (2005) Maternal influenza infection is likely to alter fetal brain development indirectly: the virus is not detected in the fetus. Int J Dev Neurosci 23:299–305.

    Article  PubMed  Google Scholar 

  • Shi L, Smith SE, Malkova N, Tse D, Su Y, Patterson PH (2008) Activation of the maternal immune system alters cerebellar development in the offspring Brain Behav Immun. Aug 9 [Epub ahead of print].

    Google Scholar 

  • Singh VK, Warren RP, Odell JD, Cole P (1991) Changes of soluble interleukin-2, interleukin-2 receptor, T8 antigen, and interleukin-1 in the serum of autistic children. Clin Immunol Immunopathol 61:448–455.

    Article  PubMed  CAS  Google Scholar 

  • Smith SE, Li J, Garbett K, Mirnics K, Patterson PH (2007) Maternal immune activation alters fetal brain development through interleukin-6. J Neurosci 27:10695–10702.

    Article  PubMed  CAS  Google Scholar 

  • Theoharides TC, Weinkauf C, Conti P (2004) Brain cytokines and neuropsychiatric disorders. J Clin Psychopharmacol 24:577–581.

    Article  PubMed  Google Scholar 

  • Tsuda N, Eda T, Mizuno M, Sotoyama H, Nawa H (2007) Minocycline improves cognitive and behavioral impairments resulted from neonatal exposure to interleukin-1. 2007 Society for Neuroscience poster presentation.

    Google Scholar 

  • Turetsky BI, Calkins ME, Light GA, Olincy A, Radant AD, Swerdlow NR (2007) Neurophysiological Endophenotypes of Schizophrenia: The Viability of Selected Candidate Measures. Schizophr Bull 33:69–94.

    Article  PubMed  Google Scholar 

  • Urakubo A, Jarskog LF, Lieberman JA, Gilmore JH (2001) Prenatal exposure to maternal infection alters cytokine expression in the placenta, amniotic fluid, and fetal brain. Schizophr Res 47:27–36.

    Article  PubMed  CAS  Google Scholar 

  • Vargas DL, Nascimbene C, Krishnan C, Zimmerman AW, Pardo CA (2005) Neuroglial activation and neuroinflammation in the brain of patients with autism. Ann Neurol 57:67–81.

    Article  PubMed  CAS  Google Scholar 

  • Wang X, Rousset CI, Hagberg H, Mallard C (2006) Lipopolysaccharide-induced inflammation and perinatal brain injury. Semin Fetal Neonatal Med 11:343–353.

    Article  PubMed  Google Scholar 

  • Wang X, Hagberg H, Nie C, Zhu C, Ikeda T, Mallard C (2007) Dual role of intrauterine immune challenge on neonatal and adult brain vulnerability to hypoxia-ischemia. J Neuropathol Exp Neurol 66:552–561.

    Article  PubMed  CAS  Google Scholar 

  • Watson CG, Kucala T, Tilleskjor C, Jacobs L (1984) Schizophrenic birth seasonality in relation to the incidence of infectious diseases and temperature extremes. Arch Gen Psychiatry 41:85–90.

    PubMed  CAS  Google Scholar 

  • Weiner I (2003) The “two-headed” latent inhibition model of schizophrenia: modeling positive and negative symptoms and their treatment. Psychopharmacology (Berl) 169:257–297.

    Article  CAS  Google Scholar 

  • Weinstock M (2001) Alterations induced by gestational stress in brain morphology and behaviour of the offspring. Prog Neurobiol 65:427–451.

    Google Scholar 

  • Zhang XY, Zhou DF, Cao LY, Wu GY, Shen YC (2005) Cortisol and cytokines in chronic and treatment- resistant patients with schizophrenia: association with psychopathology and response to antipsychotics. Neuropsychopharmacology 30:1532–1538.

    Article  PubMed  CAS  Google Scholar 

  • Zimmerman AW, Jyonouchi H, Comi AM, Connors SL, Milstien S, Varsou A, Heyes MP (2005) Cerebrospinal fluid and serum markers of inflammation in autism. Pediatr Neurol 33:195–201.

    Article  PubMed  Google Scholar 

  • Zuckerman L, Weiner I (2005) Maternal immune activation leads to behavioral and pharmacological changes in the adult offspring. J Psychiatr Res 39:311–323.

    Article  PubMed  Google Scholar 

  • Zuckerman L, Rehavi M, Nachman R, Weiner I (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 28:1778–1789.

    Article  PubMed  CAS  Google Scholar 

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  1. Biology Division, California Institute of Technology, Pasadena, CA 91125, USA

    Paul H. Patterson

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  1. Stephen E.P. Smith
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  1. Departments of Neurology and Neuroscience and Psychiatry, University of Medicine and Dentistry of New Jersey — NJ Medical School, Newark, NJ 07103, USA

    Allan Siegel

  2. University of Medicine and Dentistry of New Jersey — NJ Medical School, Newark, NJ 07103, USA

    Steven S. Zalcman

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Smith, S.E., Patterson, P.H. (2009). Alteration of Neurodevelopment and behavior by Maternal Immune Activation. In: Siegel, A., Zalcman, S.S. (eds) The Neuroimmunological Basis of Behavior and Mental Disorders. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-84851-8_7

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