The DOI matches its Crossref record; 116 of the 117 references it cites were found in a registry or an index.
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
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).”
Cited by
Sorted by citations
Items 201–247 of 247
Zhang, Y., Wei, Q., Wang, Y., Zeng, L., Sun, S., Wu, Y., Ren, C., Wang, F., Chen, G., & Cao, L. (2022) · Brain and Behavior · doi:10.1002/brb3.2817 · Cited by 2
“However, due to significant changes in the endocrine and immune systems of the body, pregnancy also increases the sensitivity to adverse factors and especially increases the risk of infection (Oskvig et al., 2012).”
BackgroundFontes‐Dutra, M., Rabelo, B. F., Santos‐Terra, J., Deckmann, I., Schwingel, G. B., & Gottfried, C. (2020) · Progress in inflammation research · doi:10.1007/978-3-030-39335-9_11 · Cited by 3
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. (2020) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2020.06.13.150359 · Cited by 3
“and rat MIA models, where similar pathways were down- or up-regulated in fetal brain in the hours following MIA (69,70).”
BackgroundMattei, D., Güneykaya, D., Ugursu, B., & Buonfiglioli, A. (2025) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19102-2.00028-4 · Cited by 2
Mitochondrial dysregulation as a central mechanism in autism spectrum disorder pathogenesis
Liao, X., Shao, J., & Chen, Z. (2025) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2025.578851 · Cited by 2
Otkiran, G., Erdoğan, M. A., Uyanıkgil, Y., & Erbaş, O. (2026) · Journal of Neuroimmune Pharmacology · doi:10.1007/s11481-025-10275-6 · Cited by 2
“Unlike these established poly(I: C)- and LPS-based models (Smith et al. 2007; Meyer 2014 ; Oskvig et al. 2012 ), which largely attri - bute ASD-relevant outcomes to broad inflammatory activa - tion, the present study focuses specifically on IFN-α as the immunological trigger.”
Peregud, D., Freiman, S. V., Тишкина, А. О., Sokhranyaeva, L. S., Лазарева, Н. А., Onufriev, M. V., Stepanichev, M. Y., & Gulyaeva, N. V. (2017) · Russian Journal of Genetics Applied Research · doi:10.1134/s2079059717010117 · Cited by 2
“С помощью экспрессионного анализа на полногеномном уровне установлено, что различные виды стресса (Erburu et al., 2015), включая индуцированный провоспалительными стимулами (Oskvig et al., 2012), могут сопровождаться значимыми изменениями уровня тысяч мРНК в ЦНС.”
Hardie, I., Murray, A. L., King, J. P. J., Hall, H. A., Okelo, K., Luedecke, E., Marryat, L., Thompson, L. C., Minnis, H., Lombardo, M. V., et al. (2024) · Journal of Epidemiology & Community Health · doi:10.1136/jech-2023-221826 · Cited by 2
Immune Involvement in Autism Spectrum Disorder as a Basis for Animal Models
Hsiao, E. Y. (2012) · Autism - Open Access · doi:10.4172/2165-7890.s1-003 · Cited by 2
“MIA by any of these inflammatory stimuli leads to autism- and schizophreniarelated behavioral abnormalities in the offspring (reviewed in [15-18]).”
BackgroundLai, C.-Y., Arzavala, J., Pinto‐Duarte, A., Wang, S., Li, J., Liu, H., Osteen, J. K., Castanon, R., Nery, J. R., Powell, S. B., et al. (2026) · Molecular Psychiatry · doi:10.1038/s41380-026-03856-1 · Cited by 2
Russell, I. S. B., & Perreault, M. L. (2026) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2025.12.010 · Cited by 1
Kariminejad-Farsangi, H., Kariminejad-Farsangi, H., Rajizadeh, M. A., Abbaspoor, M., Mohammadipoor‐Ghasemabad, L., Joushi, S., & Sheibani, V. (2026) · Scientific Reports · doi:10.1038/s41598-026-40163-9 · Cited by 1
From maternal metabolism to offspring brain: how high-fructose diets shape neurodevelopment
Vallés, A. S., Spalm, F. H. P., & Sánchez, M. L. C. (2026) · Trends in Neurosciences · doi:10.1016/j.tins.2026.03.006 · Cited by 1
Sex-specific outcomes following chorioamnionitis
Knobbe, J. E., & Bermick, J. (2026) · Pediatric Research · doi:10.1038/s41390-026-05336-2 · Cited by 1
Foley, K. A. (2013) · Scholarship@Western (Western University) · Cited by 1
Sabaghi, A., Heyrani, A., Kiani, A., & Yousofvand, N. (2019) · The Neuroscience Journal of Shefaye Khatam · doi:10.29252/shefa.7.1.43 · Cited by 1
The influence of maternal high-fat diet consumption on neurobehavioral development
Mitchell, A. J., Selby, M., & Sullivan, E. L. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-817986-4.00051-1 · Cited by 1
Immunotoxicity in Autism Spectrum Disorders
DeWitt, J. C., & Dietert, R. R. (2013) · Springer eBooks · doi:10.1007/978-1-4614-4788-7_91 · Cited by 1
Nguyen, A. (2016) · ERA: Education and Research Archive (University of Alberta) · doi:10.7939/r3057d35z · Cited by 1
Yotova, A. Y., Li, L., O’Leary, A., Tegeder, I., Reif, A., Courtney, M. J., Slattery, D. A., & Freudenberg, F. (2023) · Research Square · doi:10.21203/rs.3.rs-3100753/v1 · Cited by 1
Inflammation and immune-mediated neurobehavioral alterations : a critical role for microglia
Lacabanne, C. (2018) · theses.fr (ABES) · doi:10.70675/41a4e2a3zdbb7z4aa0z899dz9553bb07954b · Cited by 1
Fernández‐López, D., & Vexler, Z. S. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8915-3_9
Debarba, L. K. (2012) · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas)
Flinkkilä, E. (2015) · Työväentutkimus Vuosikirja
Nguyen, A. (2014) · John Spoor Broome Library Institutional Repository (California State University)
An Investigation of Short-Term Memory Functioning in a Neurodevelopmental Rat Model of Schizophrenia
Moyett, A. (2015) · Seton Hall University eRepository (Seton Hall University)
Tobacco addiction in individuals with schizophrenia: A study in rats
Waterhouse, U. (2016) · doi:10.26686/wgtn.17019920.v1
“Thus, it is generally accepted that the resulting changes in brain and behaviour of the offspring are the result of the activation of the maternal immune system (Ashdown et al., 2006; Oskvig et al., 2012).”
BackgroundPerinatal programming of metabolic dysfunction and obesity-induced inflammation
Ingvorsen, C., Hellgren, L. I., & Brix, S. (2013)
Wheeler, R. V. (2018) · DalSpace (Dalhousie University)
Early-life stress and inflammatory cytokines in psychoses: from bench to community-based research
Zuelli, F. M. D. G. C. (2020) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/d.17.2020.tde-26072019-154034
Ben‐Ari, Y. (2019) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.733499087.793568939
The dual hit hypothesis of schizophrenia
Guerrin, C. G. J. (2023) · University of Groningen research database (University of Groningen / Centre for Information Technology) · doi:10.33612/diss.791866719
“Maternal weight and body temperature (measured on the flank with an infrared thermometer, Pro’s Kit, MT-4612 MT-4612 ) were”
Santos‐Silva, T. (2023) · Digital Library of Theses and Dissertations (Universidade de São Paulo) · doi:10.11606/t.17.2023.tde-10112023-160657
Yotova, A. Y. (2024) · Publication Server of Goethe University Frankfurt am Main (Goethe University Frankfurt) · doi:10.21248/gups.85791
Lcn2 deficiency leads to social impairments independent of maternal immune activationPreprint
Pękała, M., Zawiślak, S., Romanis, S., Nader, K., Cabaj, A., Madecka, A., Puścian, A., Knapska, E., Pawlak, R., Kaczmarek, L., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.06.27.661499
Lcn2 deficiency leads to long-lasting social impairments independent of maternal immune activation
Pekala, M., Zawiślak, S., Romanis, S., Nader, K., Dzwonek, J., Cabaj, A., Madecka, A., Puścian, A., Knapska, E., Pawlak, R., et al. (2026) · Journal of Neuroinflammation · doi:10.1186/s12974-026-03742-1
“These findings are in line with previous MIA transcriptomic studies identifying genes in specific categories related to central nervous system development [112–114].”
Novais, A. R. B. (2012) · theses.fr (ABES) · doi:10.70675/1f22637fz3f72z44b1zb311zb48edc101c77
Myelin Matters in Schizophrenia : Neurobiological Insights from Rat Model and Human Studies
Maas, D. A. (2019) · theses.fr (ABES) · doi:10.70675/4ea9aa0azc70cz4bb4zada7z4f82cac02e1c
Ben‐Azu, B., Friday, F. B., Iwhiwhu, P., & Oyovwi, O. M. (2026) · Molecular Neurobiology · doi:10.1007/s12035-026-05791-2
Ma, X., Jia, W., Zhang, X., & Shi, Y. (2026) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2026.101253
“Consistent with prior reports, prenatal LPS alone caused behavioral changes (Oskvig et al., 2012; Fern ´ andez de Cossío et al., 2017) but only modest alterations in myelination in our study, whereas combined LPS exposure and hypoxia led to a pronounced delay in myelination, supporting the concept…”
Fibrinogen as a Driver of Oxidative Stress and Apoptosis in the Fetal Brain After Maternal InfluenzaPreprint
Gonzalez-Ricon, R., Rigal, F. J., Chalen, I., & Antonson, A. M. (2026) · Research Square · doi:10.21203/rs.3.rs-10396951/v1
“This pattern is broadly consistent with prior evidence suggesting that male offspring show greater susceptibility to adverse neurodevelopmental consequences following prenatal inflammatory challenge 161,162 , although the magnitude and nature of these effects vary across models 99,152,163,164 .”
Gouveia, H. J. C. B., Manhães‐de‐Castro, R., dos Santos, O. H., da Silva‐Araújo, E. R., de Lemos, M. D. T. B., Rodrigues, T. D. O., Aïn, S. A., & Toscano, A. E. (2026) · Archives of Medical Research · doi:10.1016/j.arcmed.2026.103502
Alaskar, M. K., Alonazi, M. A., Bacha, A. G. B., Alamri, A. M., Abuaish, S., Aloudah, H. S., Alahmed, M. F., Almnaizel, A. T., & El‐Ansary, A. K. (2026) · Translational Neuroscience · doi:10.1515/tnsci-2025-0402
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
