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Maternal immune activation by LPS selectively alters specific gene expression profiles of interneuron migration and oxidative stress in the fetus without triggering a fetal immune response
Open accessAbstract
Maternal immune activation (MIA) is a risk factor for the development of schizophrenia and autism. Infections during pregnancy activate the mother's immune system and alter the fetal environment, with consequential effects on CNS function and behavior in the offspring, but the cellular and molecular links between infection-induced altered fetal development and risk for neuropsychiatric disorders are unknown. We investigated the immunological, molecular, and behavioral effects of MIA in the offspring of pregnant Sprague-Dawley rats given an intraperitoneal (0.25 mg/kg) injection of lipopolysaccharide (LPS) on gestational day 15. LPS significantly elevated pro-inflammatory cytokine levels in maternal serum, amniotic fluid, and fetal brain at 4 h, and levels decreased but remained elevated at 24 h. Offspring born to LPS-treated dams exhibited reduced social preference and exploration behaviors as juveniles and young adults. Whole genome microarray analysis of the fetal brain at 4 h post maternal LPS was performed to elucidate the possible molecular mechanisms by which MIA affects the fetal brain. We observed dysregulation of 3285 genes in restricted functional categories, with increased mRNA expression of cellular stress and cell death genes and reduced expression of developmentally-regulated and brain-specific genes, specifically those that regulate neuronal migration of GABAergic interneurons, including the Distal-less (Dlx) family of transcription factors required for tangential migration from progenitor pools within the ganglionic eminences into the cerebral cortex. Our results provide a novel mechanism by which MIA induces the widespread down-regulation of critical neurodevelopmental genes, including those previously associated with autism.
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“Gene expression alterations also involve neuronal migration processes [128] that could underlie observed cortical layering defects, characterized by a 24% increase in neuron numbers in cortical layers II/III [131].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [128]
In the citing paper
“MIA strongly upregulates cell cycle gene expression and cell proliferation, and may cause brain overgrowth [127–129].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [128]
In the citing paper
“Both poly(I:C) and LPS affect maternal cytokine signaling (e.g., interleukin-6) that passes through the placenta to affect fetal brain development31”
From Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder (2018) · cites this paper as [31]
In the citing paper
“Maternal infection is a primary environmental risk factor for ASD based on numerous epidemiological, clinical and animal studies (93–98).”
From Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder (2017) · cites this paper as [93]
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Citations
Cites
Advances in autism genetics: on the threshold of a new neurobiology
Abrahams, B. S., & Geschwind, D. H. (2008) · Nature Reviews Genetics · doi:10.1038/nrg2346 · Cited by 1,866 · cited 1×
“In addition, the placenta itself reacts strongly to MIA both morphologically and immunologically and likely contributes to fetal distress (Abrahams and Geschwind, 2008; Carpentier et al., 2011; Fatemi et al., 2011; Girard et al., 2010; Hauguel-de Mouzon and Guerre-Millo, 2006; Hsiao and Patterson,…”
Maternal Immune Activation Alters Fetal Brain Development through Interleukin-6
Smith, S. E. P., Li, J., Garbett, K., Mirnics, K., & Patterson, P. H. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.2178-07.2007 · Cited by 1,605 · cited 3×
“…perturb brain development remain unknown, but blocking the actions of the specific cytokines such as IL-6 or IL-1βprevents MIA-induced behavioral and physiological consequences in mouse offspring, offering further support for the cytokine hypothesis (Girard et al., 2010; Smith et al., 2007).”
Bellot, G., Garcia-Medina, R., Gounon, P., Chiche, J., Roux, D., Pouysségur, J., & Mazure, N. M. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00166-09 · Cited by 1,501 · cited 1×
“Bnip3 is a prominent and early responding hypoxia-induced cell death gene (Chinnadurai et al., 2008), and silencing of the gene using an siRNA suppresses hypoxia-induced autophagy (Bellot et al., 2009).”
Interneuron Migration from Basal Forebrain to Neocortex: Dependence on Dlx Genes
Anderson, S. A., Eisenstat, D. D., Shi, L., & Rubenstein, J. L. R. (1997) · Science · doi:10.1126/science.278.5337.474 · Cited by 1,462 · cited 2×
“Tangential migration from the ganglionic eminences to the cortex and hippocampus is virtually absent in double Dlx1/2 knock-out mice (Anderson et al., 1997; Cobos et al., 2005), whereas migration is fairly intact in single Dlx1 or Dlx2 knock-outs, but the mutants have fewer total numbers of…”
Autism spectrum disorders: developmental disconnection syndromes
Geschwind, D. H., & Levitt, P. (2007) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2007.01.009 · Cited by 1,411 · cited 1×
“Already evidence is surfacing to show that improper cortical interneuron development and function may play a role in maladaptive social behaviors associated with autism and schizophrenia (Belforte et al., 2009; Geschwind and Levitt, 2007; Levitt, 2005).”
Signal transduction by the lipopolysaccharide receptor, Toll-like receptor-4
Pålsson‐McDermott, E. M., & O'Neill, L. A. J. (2004) · Immunology · doi:10.1111/j.1365-2567.2004.01976.x · Cited by 1,254 · cited 1×
“The resulting activation of the transcription factor NF-κB induces pro-inflammatory cytokine expression (Palsson-McDermott and O'Neill, 2004).”
Welch, W. J. (1992) · Physiological Reviews · doi:10.1152/physrev.1992.72.4.1063 · Cited by 1,190 · cited 1×
“Members of the heat shock family of proteins, which respond to cellular stress signals including oxidative stress and hypoxia (Chi and Karliner, 2004; Tucker et al., 2011; Welch, 1992) were also significantly up-regulated in fetal brain further suggestive of intermittent fetal hypoxia.”
Serologic Evidence of Prenatal Influenza in the Etiology of Schizophrenia
Brown, A. S., Begg, M. D., Gravenstein, S., Schaefer, C. A., Wyatt, R. J., Bresnahan, M. A., Babulas, V. P., & Susser, E. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.8.774 · Cited by 1,048 · cited 2×
“, 2010; Ciaranello and Ciaranello, 1995) and schizophrenia (Brown et al., 2004).”
Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring
Shi, L., Fatemi, S. H., Sidwell, R. W., & Patterson, P. H. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-01-00297.2003 · Cited by 1,025 · cited 2×
“, 2007), influenza (Shi et al., 2003), or Borna disease virus (Pletnikov et al.”
Cytokines and the nervous system II: actions and mechanisms of action
Rothwell, N. J., & Hopkins, S. J. (1995) · Trends in Neurosciences · doi:10.1016/0166-2236(95)93890-a · Cited by 922 · cited 1×
“Cytokines are a class of secreted polypeptides that have diverse functions (Benveniste, 1998; Patterson and Nawa, 1993; Rothwell and Hopkins, 1995).”
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Knuesel, I., Chicha, L., Britschgi, M., Schobel, S. A., Bodmer, M., Hellings, J. A., Toovey, S., & Prinssen, E. P. (2014) · Nature Reviews Neurology · doi:10.1038/nrneurol.2014.187 · Cited by 880
The role of inflammation in perinatal brain injury
Hagberg, H., Mallard, C. E., Ferriero, D. M., Vannucci, S. J., Levison, S. W., Vexler, Z. S., & Gressèns, P. (2015) · Nature Reviews Neurology · doi:10.1038/nrneurol.2015.13 · Cited by 852
Fillman, S. G., Cloonan, N., Catts, V. S., Miller, L. C., Wong, J., McCrossin, T., Cairns, M., & Weickert, C. S. (2013) · Molecular Psychiatry · doi:10.1038/mp.2012.110 · Cited by 609
Emerging Roles for the Gut Microbiome in Autism Spectrum Disorder
Vuong, H. E., & Hsiao, E. Y. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.08.024 · Cited by 595
Hanamsagar, R., Alter, M. D., Block, C. S., Sullivan, H., Bolton, J. L., & Bilbo, S. D. (2017) · Glia · doi:10.1002/glia.23176 · Cited by 384
The ASD Living Biology: from cell proliferation to clinical phenotype
Courchesne, E., Pramparo, T., Gazestani, V. H., Lombardo, M. V., Pierce, K., & Lewis, N. E. (2019) · Molecular Psychiatry · doi:10.1038/s41380-018-0056-y · Cited by 333
Hanamsagar, R., Alter, M. D., Block, C. L., Sullivan, H. K., Bolton, J. L., & Bilbo, S. D. (2017) · Glia · doi:10.1002/glia.23277 · Cited by 297
Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero
al-Haddad, B. J. S., Jacobsson, B., Chabra, S., Modzelewska, D., Olson, E. M., Bernier, R., Enquobahrie, D. A., Hagberg, H., Östling, S., Rajagopal, L., et al. (2019) · JAMA Psychiatry · doi:10.1001/jamapsychiatry.2019.0029 · Cited by 289
Inflammation and the two-hit hypothesis of schizophrenia
Feigenson, K. A., Kusnecov, A., & Silverstein, S. M. (2013) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2013.11.006 · Cited by 293
Brain changes in a maternal immune activation model of neurodevelopmental brain disorders
Bergdolt, L., & Dunaevsky, A. (2018) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2018.12.002 · Cited by 282
“paired neuronal migration in MIA offspring, gene expression of several proteins involved in tangential migration of interneurons was reduced in the fetal brain four hours after LPS administration (Oskvig et al., 2012).”
The fetal origins of mental illness
al-Haddad, B. J. S., Oler, E., Armistead, B., Elsayed, N. A., Weinberger, D. R., Bernier, R., Burd, I. D., Kapur, R. P., Jacobsson, B., Wang, C., et al. (2019) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2019.06.013 · Cited by 272
Tylee, D. S., Sun, J., Hess, J. L., Tahir, M. A., Sharma, E., Malik, R., Worrall, B. B., Levine, A. J., Martinson, J. J., Nejentsev, S., et al. (2018) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32652 · Cited by 219
“…changes during early brain development and in fully developed adults have been identified (Deverman & Patterson, 2009; Felger & Lotrich, 2013; Meyer, 2014; Miller, Haroon, Raison, & Felger, 2013; Oskvig et al., 2012; Sekar et al., 2016; Shatz, 2009; Smith, Li, Garbett, Mirnics, & Patterson, 2007).”
Neuroinflammation and Oxidative Stress in the Pathogenesis of Autism Spectrum Disorder
Usui, N., Kobayashi, H., & Shimada, S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24065487 · Cited by 278
“MIA-affected placental histopathology and oxidative stress such as cyclooxygenase-2 (COX-2) and malondialdehyde can impair nutritional supply from the mother and placenta to the fetus in mice [84,86].”
BackgroundOxidative Stress‐Related Mechanisms in Schizophrenia Pathogenesis and New Treatment Perspectives
Ermakov, E. A., Dmitrieva, E. M., Parshukova, D. A., Kazantseva, D. V., Vasilieva, A. R., & Smirnova, L. P. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/8881770 · Cited by 256
“confirm that lipopolysaccharide- (LPS-) induced maternal immune activation leads to an increase of expression profiles of oxidative stress-related genes and a decrease of expression profiles of critical neurodevelopmental genes in the fetal brain [114].”
BackgroundGérardin, P., Sampériz, S., Ramful, D., Boumahni, B., Bintner, M., Alessandri, J., Carbonnier, M., Tiran-Rajaofera, I., Beullier, G., Boya, I., et al. (2014) · PLoS neglected tropical diseases · doi:10.1371/journal.pntd.0002996 · Cited by 241
“Maternal hyperthermia and pro-inflammatory cytokines have been consistently demonstrated in small animal models to affect apoptosis, perturbation of neuronal migration into the neocortex and down regulation of brain-specific genes involved in behavioral changes in the offspring [31,32].”
BackgroundPrenatal infection leads to ASD-like behavior and altered synaptic pruning in the mouse offspring
de Cossío, L. F., Guzman, A. S., van der Veldt, S., & Luheshi, G. N. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.09.028 · Cited by 227
“A number of environmental (Estes and McAllister, 2015) and genetic (Oskvig et al., 2012; Sullivan et al., 2012) factors, as well as their interaction, have been suggested to disrupt neuronal structure and function, which can ultimately result in disorders like Schizophrenia,…”
BackgroundGumusoglu, S. B., & Stevens, H. E. (2018) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.08.008 · Cited by 216
Lombardo, M. V., Moon, H. M., Su, J., Palmer, T. D., Courchesne, E., & Pramparo, T. (2018) · Molecular Psychiatry · doi:10.1038/mp.2017.15 · Cited by 201
“31 This dataset applied a LPS manipulation for the MIA-inducing event on gestational day 15, which in humans corresponds to near the end of the first trimester of pregnancy.”
InfluentialNoh, H., Jeon, J., & Seo, H. (2014) · Neurochemistry International · doi:10.1016/j.neuint.2014.02.008 · Cited by 216
Programming Bugs: Microbiota and the Developmental Origins of Brain Health and Disease
Codagnone, M. G., Spichak, S., O’Mahony, S. M., O’Leary, O. F., Clarke, G., Stanton, C., Dinan, T. G., & Cryan, J. F. (2019) · Biological Psychiatry · doi:10.1016/j.biopsych.2018.06.014 · Cited by 198
“Though there exists no current research of its impa ct on the microbiota, the bacterial mimetic lipopolysaccharide can also induce behavioral pheno types for anxiety, depression, or autism spectrum disorder in offspring (109, 110); impairme nts in hippocampal development and neurogenesis (111, 112); and increased post…”
BackgroundHaddad, F. L., Patel, S. V., & Schmid, S. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2020.04.012 · Cited by 206
Translational evaluation of translocator protein as a marker of neuroinflammation in schizophrenia
Notter, T., Coughlin, J. M., Gschwind, T., Weber‐Stadlbauer, U., Wang, Y., Kassiou, M., Vernon, A. C., Benke, D., Pomper, M. G., Sawa, A., et al. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.248 · Cited by 200
Cortical interneurons in autism
Contractor, A., Ethell, I. M., & Portera‐Cailliau, C. (2021) · Nature Neuroscience · doi:10.1038/s41593-021-00967-6 · Cited by 186
Inflammation in schizophrenia: A question of balance
Leza, J. C., García‐Bueno, B., Bioque, M., Arango, C., Parellada, M., Kim, Q., O’Donnell, P., & Bernardo, M. (2015) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2015.05.014 · Cited by 188
Oxidative stress, prefrontal cortex hypomyelination and cognitive symptoms in schizophrenia
Maas, D. A., Vallès, A., & Martens, G. J. M. (2017) · Translational Psychiatry · doi:10.1038/tp.2017.138 · Cited by 183
Weber-Stadlbauer, U., Richetto, J., Labouesse, M. A., Bohacek, J., Mansuy, I. M., & Meyer, U. (2017) · Molecular Psychiatry · doi:10.1038/mp.2016.41 · Cited by 170
Implications for reactive oxygen species in schizophrenia pathogenesis
Koga, M., Serritella, A. V., Sawa, A., & Sedlak, T. W. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.06.022 · Cited by 164
“Maternal immune activation also alters mRNA expression of genes that regulate migration of GABA interneurons from ganglionic eminences to the cortex, including the Distal-less (Dlx) family of transcription factors (Oskvig et al., 2012).”
BackgroundNotaras, M., Lodhi, A., Dündar, F., Collier, P., Sayles, N. M., Tilgner, H., Greening, D., & Colak, D. (2022) · Molecular Psychiatry · doi:10.1038/s41380-021-01316-6 · Cited by 150
“MIA Scz models have reported increased cell death [20] as well as delayed axon development [21], and have also unveiled alterations in tonic”
BackgroundCOVID-19 in pregnancy: implications for fetal brain development
Shook, L. L., Sullivan, E. L., Lo, J. O.-T., Perlis, R. H., & Edlow, A. G. (2022) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2022.02.004 · Cited by 146
“(iv) Maternal and placental immune activation are associated with placental and fetal brain mitochondrial dysfunction, oxidative stress, and disrupted protein homeostasis [88,91,104,105].”
Madore, C., Leyrolle, Q., Lacabanne, C., Benmamar-Badel, A., Joffre, C., Nadjar, A., & Layé, S. (2016) · Neural Plasticity · doi:10.1155/2016/3597209 · Cited by 141
“This could be linked to altered expression of neuronal migration genes [100] or to defects in synaptic pruning and synaptogenesis with a plausible involvement of microglia [45].”
BackgroundThe role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness
Hornig, M. (2013) · Current Opinion in Rheumatology · doi:10.1097/bor.0b013e32836208de · Cited by 138
Foley, K. A., Ossenkopp, K., Kavaliers, M., & MacFabe, D. F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087072 · Cited by 135
“Assessment of open-field activity has yielded mixed results, with decreased nose-hole pokes [27] and decreased activity and centre entries [28], no change in locomotor activity [27], [29], or increased activity [30] being observed.”
ResultMissault, S., Van den Eynde, K., Vanden Berghe, W., Fransen, E., Weeren, A., Timmermans, J. P., Kumar-Singh, S., & Dedeurwaerdere, S. (2014) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2014.06.013 · Cited by 128
“While many studies have described increases in inflammatory cytokine protein levels in the foetal brain after MIA challenges (Poly I:C, LPS), they could often not find any difference in inflammatory cytokine mRNA expression, leading to the assumption that the increased cytokines are not derived from the foetus, but or…”
BackgroundWong, H., & Hoeffer, C. A. (2017) · Experimental Neurology · doi:10.1016/j.expneurol.2017.04.010 · Cited by 131
“…has been induced in pregnant mice using several approaches, including direct infection or exposure to lipopolysaccharide (LPS) to mimic bacterial infection or poly(I:C) to mimic viral infection (Choi et al., 2016; Oskvig et al., 2012; Shi et al., 2003; Shi et al., 2009; Smith et al., 2007).”
MethodThe role of IL-6 in neurodevelopment after prenatal stress
Gumusoglu, S. B., Fine, R. S., Murray, S. J., Bittle, J. L., & Stevens, H. E. (2017) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2017.05.015 · Cited by 129
Gut Microbiota, Inflammation, and Probiotics on Neural Development in Autism Spectrum Disorder
Doenyas, C. (2018) · Neuroscience · doi:10.1016/j.neuroscience.2018.01.060 · Cited by 123
Inflammation and the developing brain: Consequences for hippocampal neurogenesis and behavior
Green, H. F., & Nolan, Y. M. (2014) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2014.01.004 · Cited by 118
Immune system gene dysregulation in autism and schizophrenia
Michel, M., Schmidt, M. J., & Mirnics, K. (2012) · Developmental Neurobiology · doi:10.1002/dneu.22044 · Cited by 107
“This finding was extended to show that exposure to an analogue of bacterial infection (lipopolysaccharide, LPS) led to elevation of cytokine levels in the fetal brain and maternal circulation, but did not result in altered cytokine mRNA synthesis in the fetal brain, suggesting a maternal and not fetal immune response…”
Prenatal stress delays inhibitory neuron progenitor migration in the developing neocortex
Stevens, H. E., Su, T., Yanagawa, Y., & Vaccarino, F. M. (2012) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.07.011 · Cited by 105
“While other prenatal environmental exposures with relevance for later behavioral disorders have been shown to alter transcription factors of the ganglionic eminence (Godin et al., 2011; Oskvig et al., 2012), this is the first data showing that prenatal stress affects early regulators of cortical inhibitory neurons.”
BackgroundMaternal Low-Grade Chronic Inflammation and Intrauterine Programming of Health and Disease
Parisi, F., Milazzo, R., Savasi, V. M., & Cetin, I. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041732 · Cited by 117
“As an example, controversial increases in TNFα, IL-1, and IL-6 have been detected in fetal liver, brain, and plasma after maternal lipopolysaccharide (LPS) injection, but the gestational age and timing of injection need to be considered as impacting placental transport capacity [65,66].”
BackgroundToward a Better Understanding of Neuronal Migration Deficits in Autism Spectrum Disorders
Pan, Y.-H., Wu, N., & Yuan, X. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00205 · Cited by 100
“, 2016), neuronal migration deficits are prominent features (Kuwagata et al., 2009; Oskvig et al., 2012).”
BackgroundFoley, K. A., MacFabe, D. F., Kavaliers, M., & Ossenkopp, K. (2014) · Behavioural Brain Research · doi:10.1016/j.bbr.2014.09.032 · Cited by 100
Prenatal stress and inhibitory neuron systems: implications for neuropsychiatric disorders
Fine, R., Zhang, J., & Stevens, H. E. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.35 · Cited by 96
Molecular substrates of schizophrenia: homeostatic signaling to connectivity
Landek‐Salgado, M. A., Faust, T. E., & Sawa, A. (2015) · Molecular Psychiatry · doi:10.1038/mp.2015.141 · Cited by 95
Toward an immune-mediated subtype of autism spectrum disorder
McDougle, C. J., Landino, S. M., Vahabzadeh, A., O’Rourke, J., Zurcher, N. R., Finger, B. C., Palumbo, M. L., Helt, J., Mullett, J. E., Hooker, J. M., et al. (2015) · Brain Research · doi:10.1016/j.brainres.2014.09.048 · Cited by 95
The connection between microbiome and schizophrenia
Golofast, B., & Vales, K. (2020) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2019.12.011 · Cited by 92
Vasistha, N. A., Pardo-Navarro, M., Gasthaus, J., Weijers, D., Müller, M., García‐González, D., Malwade, S., Korshunova, I., Pfisterer, U., von Engelhardt, J., et al. (2019) · Molecular Psychiatry · doi:10.1038/s41380-019-0539-5 · Cited by 96
Jiang, Z., Cowell, R. M., & Nakazawa, K. (2013) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2013.00116 · Cited by 91
“…enzymes and antioxidants have been reported in schizophrenia (Suboticanec et al., 1990; Reddy et al., 1991; McCreadie et al., 1995; Mukerjee et al., 1996; Yao et al., 1998, 2000; Do et al., 2000; Ranjekar et al., 2003; Reddy et al., 2003; Yao et al., 2006; Dadheech et al., 2008; Raffa et al.,…”
BackgroundSimões, L. R., Sangiogo, G., Tashiro, M. H., Generoso, J. S., Faller, C. J., Dominguini, D., Mastella, G. A., Scaini, G., Giridharan, V. V., Michels, M., et al. (2018) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2018.02.007 · Cited by 89
Innate Immune Regulation by Toll-Like Receptors in the Brain
Mallard, C. E. (2012) · ISRN Neurology · doi:10.5402/2012/701950 · Cited by 82
“In this study, maternal LPS induced dysregulation of genes in the fetal brain belonging to specific functional categories, including increased mRNA expression of cellular stress and cell death genes and reduced expression of developmentally regulated and brain-specific genes, specifically those that regulate neuronal…”
BackgroundThe dual hit hypothesis of schizophrenia: Evidence from animal models
Guerrin, C. G. J., Doorduin, J., Sommer, I. E., & de Vries, E. F. J. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.10.025 · Cited by 87
Woods, R. M., Lorusso, J. M., Fletcher, J., ElTaher, H., McEwan, F., Harris, I., Kowash, H. M., D'Souza, S. W., Harte, M., Hager, R., et al. (2023) · Neuronal Signaling · doi:10.1042/ns20220064 · Cited by 87
The effect of maternal Inflammation on foetal programming of metabolic disease
Ingvorsen, C., Brix, S., Ozanne, S. E., & Hellgren, L. I. (2015) · Acta Physiologica · doi:10.1111/apha.12533 · Cited by 81
Child neurodevelopmental outcomes following preterm and term birth: what can the placenta tell us?
Hodyl, N. A., Aboustate, N., Bianco-Miotto, T., Roberts, C. T., Clifton, V. L., & Stark, M. J. (2017) · Placenta · doi:10.1016/j.placenta.2017.06.009 · Cited by 76
Bordeleau, M., Carrier, M., Luheshi, G. N., & Tremblay, M.-È. (2019) · Seminars in Cell & Developmental Biology · doi:10.1016/j.semcdb.2019.06.001 · Cited by 75
Cieślik, M., Gąssowska-Dobrowolska, M., Jęśko, H. M., Czapski, G. A., Wilkaniec, A., Zawadzka, A., Dominiak, A., Polowy, R., Filipkowski, R. K., Boguszewski, P. M., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21114097 · Cited by 77
Talukdar, P. M., Abdul, F., Maes, M. H. J., Binu, V. S. N., Venkatasubramanian, G., Kutty, B. M., & Debnath, M. (2020) · Molecular Neurobiology · doi:10.1007/s12035-020-02028-8 · Cited by 72
Woods, R. M., Lorusso, J. M., Potter, H. G., Neill, J. C., Glazier, J. D., & Hager, R. (2021) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2021.07.015 · Cited by 77
“Model abbreviations: M-PIC – mouse-poly(I:C); R-PIC – rat-poly(I:C); M-LPS – mouse-LPS; R-LPS – rat-LPS.”
InfluentialForrest, C. M., Khalil, O. S., Pisar, M., Smith, R. A., Darlington, L. G., & Stone, T. W. (2012) · Molecular Brain · doi:10.1186/1756-6606-5-22 · Cited by 72
“[68] have noted that cytokine protein levels are increased within the foetal brain whereas the corresponding RNA molecules are not, implying that the foetal proteins are derived from the maternal circulation and not from foetal synthesis.”
BackgroundVogel Ciernia, A., Careaga, M., LaSalle, J. M., & Ashwood, P. (2018) · Glia · doi:10.1002/glia.23261 · Cited by 69
Baines, K. J., Hillier, D. M., Haddad, F. L., Rajakumar, N., Schmid, S., & Renaud, S. J. (2020) · Frontiers in Immunology · doi:10.3389/fimmu.2020.01145 · Cited by 73
“In support of this possibility, increased brain volume, head circumference, and number of cortical neurons are found in a subset of patients diagnosed with ASD (55, 56).”
BackgroundInfluentialZuelli, F. M. D. G. C., Brognara, F., Quirino, G. F. S., Hiroki, C. H., Fais, R. S., Del‐Ben, C. M., Ulloa, L., Salgado, H. C., Kanashiro, A., & Loureiro, C. M. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00618 · Cited by 73
“It has been observed in preclinical studies that maternal immune activation in rodents induces inflammatory cytokines (IL-1β, IL-6, TNF) and reduces anti-inflammatory cytokines (IL-10) in both the maternal fluids and in the fetal brain, inducing schizophrenia-like behaviors in the offspring (35, 40).”
BackgroundCattane, N., Vernon, A. C., Borsini, A., Scassellati, C., Endres, D., Capuron, L., Tamouza, R., Benros, M. E., Leza, J. C., Pariante, C. M., et al. (2022) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2022.02.002 · Cited by 67
Lu, X., Yan, J., Feng, D., Ye, S., Yang, T., Wei, H., Li, T., Sun, W., & Chen, J. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.634837 · Cited by 60
Kentner, A. C., Khoury, A. E., Queiroz, E. L., & MacRae, M. (2016) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.03.013 · Cited by 63
“Gestational day 15 was chosen as the time of inflammatory challenge since previous investigations have shown MIA on this day to elicit long term changes in offspring behavior (Howland et al., 2012; Oskviq et al., 2012) specific to our cognitive and social measures of interest.”
Prenatal Inflammation, Infections and Mental Disorders
Flinkkilä, E., Keski‐Rahkonen, A., MARTTUNEN, M. J., & Raevuori, A. (2016) · Psychopathology · doi:10.1159/000448054 · Cited by 62
Möller, M., Swanepoel, T., & Harvey, B. H. (2015) · ACS Chemical Neuroscience · doi:10.1021/cn5003368 · Cited by 60
Prenatal ontogeny as a susceptibility period for cortical GABA neuron disturbances in schizophrenia
Volk, D. W., & Lewis, D. A. (2013) · Neuroscience · doi:10.1016/j.neuroscience.2013.06.008 · Cited by 56
“…this hypothesis, animal models using the viral mimic poly I:C, a synthetic double-stranded RNA that binds to and activates toll-like receptor 3, have shown that maternal immune activation alters levels of multiple cytokines and CXCR4/7 in the fetal brain (Meyer et al., 2006; Oskvig et al., 2012).”
BackgroundInfluentialMale fetus susceptibility to maternal inflammation: C-reactive protein and brain development
Hunter, S. K., Hoffman, M. C., D’Alessandro, A., Noonan, K., Wyrwa, A., Freedman, R., & Law, A. J. (2019) · Psychological Medicine · doi:10.1017/s0033291719003313 · Cited by 57
Interaction between TNF-α and oxidative stress status in first-episode drug-naïve schizophrenia
Zhu, S., Zhao, L., Fan, Y., Lv, Q., Wu, K., Lang, X., Li, Z., Yi, Z., & Geng, D. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.104595 · Cited by 58
Three Decades of Valproate: A Current Model for Studying Autism Spectrum Disorder
Zárate-López, D., Torres-Chávez, A. L., Gálvez‐Contreras, A. Y., & González-Pérez, Ó. (2023) · Current Neuropharmacology · doi:10.2174/1570159x22666231003121513 · Cited by 62
“In addition, MIA involves oxidative stress and mitochondrial dysfunction [332, 333].”
BackgroundMaternal stressors and the developmental origins of neuropsychiatric risk
Khambadkone, S. G., Cordner, Z. A., & Tamashiro, K. L. (2020) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2020.100834 · Cited by 61
“At the cellular level, there is evidence for altered neurogenesis and neuronal migration, as well as alterations in microglia and astroglia (Solek et al., 2018; de Souza et al., 2015; Zhang et al., 2018; Smolders et al., 2018; Prins et al., 2018; Liu et al., 2013; Oskvig et al., 2012).”
BackgroundInfluentialImpaired Interneuron Development in a Novel Model of Neonatal Brain Injury
Lacaille, H., Vacher, C., Bakalar, D., O’Reilly, J. J., Salzbank, J., & Penn, A. A. (2019) · eNeuro · doi:10.1523/eneuro.0300-18.2019 · Cited by 55
“A prior transcriptomic study using MIA shown down-regulation of transcripts involved in interneuron tangential migration including the Distalless (Dlx) family and both GAD isoforms (Oskvig et al., 2012), suggesting that impaired migration may also play a role in the findings observed in E17.”
MethodStraley, M. E., Van Oeffelen, W., Theze, S., Sullivan, A. M., O’Mahony, S. M., Cryan, J. F., & O’Keeffe, G. W. (2017) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2016.06.002 · Cited by 52
Sarieva, K., Kagermeier, T., Khakipoor, S., Atay, E., Yentür, Z., Becker, K., & Mayer, S. (2023) · Molecular Psychiatry · doi:10.1038/s41380-023-01997-1 · Cited by 52
“Diverse animal models have shown that MIA contributes to the behavioral de fi cits that recapitulate ASD symptoms in humans [11 – 15].”
Cellular stress mechanisms of prenatal maternal stress: Heat shock factors and oxidative stress
Dowell, J., Elser, B. A., Schroeder, R. E., & Stevens, H. E. (2019) · Neuroscience Letters · doi:10.1016/j.neulet.2019.134368 · Cited by 51
“Our group and others have found that these embryonic brain processes may be sensitive to maternal inflammation [71, 142] and oxidative stress [28], for example.”
BackgroundBiomarkers for drug development in early psychosis: Current issues and promising directions
GOFF, D. C., Romero, K., Paul, J., Pérez-Rodríguez, M. M., CRANDALL, D. T., & Potkin, S. G. (2016) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2016.01.009 · Cited by 49
Batinić, B., Santrač, A., Divović, B., Stamenić, T. T., Stanković, T., Obradović, A. L., Joksimovic, S. M., & Savić, M. M. (2015) · Behavioural Brain Research · doi:10.1016/j.bbr.2015.11.025 · Cited by 51
Epigenetic dysfunctional diseases and therapy for infection and inflammation
Samanta, S., Rajasingh, S., Cao, T., Dawn, B., & Rajasingh, J. (2016) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.11.030 · Cited by 49
“Microarray studies in mice explained that maternal health including infection by both bacteria ad virus contributes to changes in expression of key developmental genes in the placenta and therefore, linked to the development of the offspring [117].”
Different Paths to Core Pathology: The Equifinal Model of the Schizophrenia Syndrome
Green, I. W., & Glausier, J. R. (2015) · Schizophrenia Bulletin · doi:10.1093/schbul/sbv136 · Cited by 46
Neuronal Cell Adhesion Molecules May Mediate Neuroinflammation in Autism Spectrum Disorder
Eve, M., Gandawijaya, J., Yang, L., & Oguro‐Ando, A. (2022) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2022.842755 · Cited by 44
Elevated Viral Restriction Factor Levels in Cortical Blood Vessels in Schizophrenia
Siegel, B. I., Sengupta, E. J., Edelson, J. R., Lewis, D. A., & Volk, D. W. (2013) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.09.019 · Cited by 42
“Furthermore, in studies that injected pregnant mice with immune-activating agents such as lipopolysaccharide or poly I:C, offspring have been shown to exhibit deficits in working memory (Oskvig et al. 2012;Meyer et al. 2008;Meyer et al. 2006;Dickerson et al. 2010).”
BackgroundGlass, R. M., Norton, S. A., Fox, N. W., & Kusnecov, A. W. (2018) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2018.05.005 · Cited by 37
Morais, L. H., Felice, D., Golubeva, A. V., Moloney, G. M., Dinan, T. G., & Cryan, J. F. (2018) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000374 · Cited by 40
“In this respect, the influenza virus, lipopolysaccharide (LPS, a cell wall component of gram-negative bacteria) and polyinosinic–polycytidylic acid [poly (I:C), a synthetic double-stranded RNA] have been administered to pregnant dams (Shi et al., 2003; Basta-Kaim et al., 2012; Oskvig et al., 2012; Hsiao et al., 2013;…”
MethodSokol, D. K., Maloney, B., Westmark, C. J., & Lahiri, D. K. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2019.00165 · Cited by 38
Sequential perturbations to mouse corticogenesis following in utero maternal immune activation
Canales, C. P., Estes, M. L., Cichewicz, K., Angara, K., Aboubechara, J. P., Cameron, S., Prendergast, K., Su-Feher, L., Zdilar, I., Kreun, E. J., et al. (2021) · eLife · doi:10.7554/elife.60100 · Cited by 43
Santos‐Silva, T., Colodete, D. A. E., Lisboa, J. R., Freitas, I. D. S., Lopes, C. F. B., Hadera, V., Lima, T. S. A., Souza, A. J., & Gomes, F. V. (2024) · Basic & Clinical Pharmacology & Toxicology · doi:10.1111/bcpt.13994 · Cited by 39
“83 Changes in PV protein expression also occur under microglial activation, negatively affecting their inhibitory function within neural networks.”
BackgroundZhu, M., Liu, Z., Guo, Y., Sultana, S., Wu, K., Lang, X., Lv, Q., Huang, X., Yi, Z., & Li, Z. (2021) · Journal of Neuroinflammation · doi:10.1186/s12974-021-02261-5 · Cited by 36
“Previous research has revealed that the mechanism of certain brain developmental disorders caused by the activation of maternal immune systems may be closely related to OxS[15].”
BackgroundThe impact of (ab)normal maternal environment on cortical development
Vasistha, N. A., & Khodosevich, K. (2021) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2021.102054 · Cited by 38
Trifiletti, R. R., Lachman, H. M., Manusama, O. R., Zheng, D., Spalice, A., Chiurazzi, P., Schornagel, A., Serban, A. M., van Wijck, R., Cunningham, J. L., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-15279-3 · Cited by 37
Pallier, P. N., Ferrara, M., Romagnolo, F., Ferretti, M. T., Soreq, H., & Cerase, A. (2022) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2022.102353 · Cited by 37
Prenatal Environment That Affects Neuronal Migration
Hwang, H. M., Ku, R. Y., & Hashimoto‐Torii, K. (2019) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2019.00138 · Cited by 35
“MATERNAL IMMUNE ACTIVATION Maternal immune activation (MIA) is caused by an infection during pregnancy, and it is linked to increased risk of ASD and schizophrenia (Patterson, 2009).”
BackgroundLasting and Sex-Dependent Impact of Maternal Immune Activation on Molecular Pathways of the Amygdala
Keever-Keigher, M. R., Zhang, P., Bolt, C. R., Antonson, A. M., Rymut, H. E., Caputo, M. P., Houser, A. K., Hernandez, A. G., Southey, B. R., Rund, L. A., et al. (2020) · Frontiers in Neuroscience · doi:10.3389/fnins.2020.00774 · Cited by 37
Page, N. F., Gandal, M. J., Estes, M. L., Cameron, S., Buth, J. E., Parhami, S., Ramaswami, G., Murray, K. D., Amaral, D. G., de Water, J. V., et al. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.10.016 · Cited by 35
Chorioamnionitis, IL‐17A, and fetal origins of neurologic disease
Lawrence, S. M., & Wynn, J. L. (2017) · American Journal of Reproductive Immunology · doi:10.1111/aji.12803 · Cited by 33
Nakamura, J., Schroeder, A., Hudson, M. R., Jones, N. C., Gillespie, B., Du, X., Notaras, M. J., Swaminathan, V., Reay, W. R., Atkins, J., et al. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.06.009 · Cited by 33
The Role of Redox Dysregulation in the Effects of Prenatal Stress on Embryonic Interneuron Migration
Bittle, J., Menezes, E. D. C., McCormick, M. L., Spitz, D. R., Dailey, M. E., & Stevens, H. E. (2019) · Cerebral Cortex · doi:10.1093/cercor/bhz052 · Cited by 33
Afroz, K. F., Reyes, N., Young, K., Parikh, K., Misra, V., & Alviña, K. (2021) · Scientific Reports · doi:10.1038/s41598-021-87678-x · Cited by 32
Fathi, M., Vakili, K. G., Yaghoobpoor, S., Qadirifard, M. S., Kosari, M., Naghsh, N., Taei, A. A., Klegeris, A., Dehghani, M., Bahrami, A., et al. (2022) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2022.855776 · Cited by 35
Dutra, M. L., Dias, P., Freiberger, V., Ventura, L., Comim, C. M., Martins, D. F., & Bobinski, F. (2022) · Neuroscience Letters · doi:10.1016/j.neulet.2022.136974 · Cited by 33
Metadata
- Authors
- Oskvig, D. B., Elkahloun, A. G., Johnson, K. R., Phillips, T. M., & Herkenham, M.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Herkenham, Miles
- Venue
- Brain, Behavior, and Immunity
- Publisher
- Elsevier BV
- Published
- 2012-05
- Volume
- 26
- Issue
- 4
- Pages
- 623-634
- ISSN
- 0889-1591 (ISSN-L)
- PMC
- PMC3285385
- OpenAlex
- W2052297858
- Cited by
- 248
- References
- 117
- Citations by year
- 2026: 13 · 2025: 9 · 2024: 16 · 2023: 22 · 2022: 23 · 2021: 19 · 2020: 21 · 2019: 21 · 2018: 19 · 2017: 15 · 2016: 19 · 2015: 15 · 2014: 14 · 2013: 13 · 2012: 9
- FWCI
- 5.07
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Brain Behavior and Immunity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Mental Health (ZIAMH001090)
- National Human Genome Research Institute (ZICHG200365)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- maternal immune activation, lipopolysaccharide, oxidative stress, inflammatory cytokines, autism risk, schizophrenia risk, social behavior, brain development, prenatal infection, cortical development
- MeSH terms
- Amniotic Fluid, Animals, Autistic Disorder, Brain, Cell Movement, Exploratory Behavior, Female, Fetus, Interneurons, Lipopolysaccharides, Pregnancy, Pregnancy Complications, Infectious, Prenatal Exposure Delayed Effects, RNA, Messenger, Social Behavior, Transcription Factors, Down-Regulation, Cytokines, Rats, Sprague-Dawley, Oxidative Stress, Gene Expression Profiling, Rats
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