The DOI matches its Crossref record; 87 of the 87 references it cites were found in a registry or an index.
Maternal immune activation induces GAD1 and GAD2 promoter remodeling in the offspring prefrontal cortex
Open accessAbstract
Maternal infection during pregnancy increases the risk of neurodevelopmental disorders in the offspring. In addition to its influence on other neuronal systems, this early-life environmental adversity has been shown to negatively affect cortical γ-aminobutyric acid (GABA) functions in adult life, including impaired prefrontal expression of enzymes required for GABA synthesis. The underlying molecular processes, however, remain largely unknown. In the present study, we explored whether epigenetic modifications represent a mechanism whereby maternal infection during pregnancy can induce such GABAergic impairments in the offspring. We used an established mouse model of prenatal immune challenge that is based on maternal treatment with the viral mimetic poly(I:C). We found that prenatal immune activation increased prefrontal levels of 5-methylated cytosines (5mC) and 5-hydroxymethylated cytosines (5hmC) in the promoter region of GAD1, which encodes the 67-kDa isoform of the GABA-synthesising enzyme glutamic acid decarboxylase (GAD67). The early-life challenge also increased 5mC levels at the promoter region of GAD2, which encodes the 65-kDa GAD isoform (GAD65). These effects were accompanied by elevated GAD1 and GAD2 promoter binding of methyl CpG-binding protein 2 (MeCP2) and by reduced GAD67 and GAD65 mRNA expression. Moreover, the epigenetic modifications at the GAD1 promoter correlated with prenatal infection-induced impairments in working memory and social interaction. Our study thus highlights that hypermethylation of GAD1 and GAD2 promoters may be an important molecular mechanism linking prenatal infection to presynaptic GABAergic impairments and associated behavioral and cognitive abnormalities in the offspring.
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
“A 2015 epigenetic study also using a single poly (I:C) injection found significantly increased rates of 5-methylcytosine and 5-hydroxymethylcytosine on the glutamic acid decarboxylase (GAD1) promoter”
From The Role of the Immune System in Autism Spectrum Disorder (2017) · cites this paper as Labouesse et al, 2015
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
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860
Shrestha, S., & Offer, S. M. (2016) · Medical Epigenetics · doi:10.1159/000444713 · Cited by 8,951
Integrative analysis of 111 reference human epigenomes
Roadmap Epigenomics Consortium, Kundaje, A., Meuleman, W., Ernst, J., Bilenky, M., Yen, A., Heravi-Moussavi, A., Kheradpour, P., Zhang, Z., Wang, J., et al. (2015) · Nature · doi:10.1038/nature14248 · Cited by 6,368
Jaenisch, R., & Bird, A. (2003) · Nature Genetics · doi:10.1038/ng1089 · Cited by 6,325
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837
Tet-Mediated Formation of 5-Carboxylcytosine and Its Excision by TDG in Mammalian DNA
He, Y., Li, B.-Z., Li, Z., Liu, P., Wang, Y., Tang, Q., Ding, J., Jia, Y., Chen, Z., Li, L., et al. (2011) · Science · doi:10.1126/science.1210944 · Cited by 2,776
Cortical inhibitory neurons and schizophrenia
Lewis, D. A., Hashimoto, T., & Volk, D. W. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1648 · Cited by 2,297
Global epigenomic reconfiguration during mammalian brain development
Lister, R., Mukamel, E. A., Nery, J. R., Urich, M., Puddifoot, C. A., Johnson, N. D., Lucero, J., Huang, Y., Dwork, A. J., Schultz, M. D., et al. (2013) · Science · doi:10.1126/science.1237905 · Cited by 1,830
MeCP2, a Key Contributor to Neurological Disease, Activates and Represses Transcription
Chahrour, M., Jung, S. Y., Shaw, C., Zhou, X., Wong, S. T. C., Qin, J., & Zoghbi, H. Y. (2008) · Science · doi:10.1126/science.1153252 · Cited by 1,823
Fabbri, M., Garzon, R., Cimmino, A., Liu, Z., Zanesi, N., Callegari, E., Liu, S., Alder, H., Costinean, S., Fernandez-Cymering, C., et al. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707628104 · Cited by 1,705
Cited by
Sorted by citations
Items 101–144 of 144
Burgio, E., Porru, A., Pettini, C., Pettini, M., Vaglini, I., Gemignani, A., Fratini, F., & Lucangeli, D. (2026) · Current Issues in Molecular Biology · doi:10.3390/cimb48020163 · Cited by 4
Deady, C., FitzGerald, J., Kara, N. Z., Mazzocchi, M., O'Mahony, A., Ionescu, M.-I., Shanahan, R., Kelly, S., Crispie, F., Cotter, P. D., et al. (2025) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2025.101065 · Cited by 4
Kawiková, I., Hakenova, K., Lebedeva, M., Kletečková, L., Jakob, L., Spicka, V., Wen, L., Španiel, F., & Valeš, K. (2024) · Physiological Research · doi:10.33549/physiolres.935501 · Cited by 5
Qiu, H., Li, H., Fan, R., Song, Y., Pan, X., Zhang, C., & Li, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232314984 · Cited by 4
Fontes‐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
Environmental Factors and Epigenetics
Weber‐Stadlbauer, U., & Richetto, J. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819641-0.00135-3 · Cited by 3
Negr1 Deficiency Modulates Sex-Specific Neurobehavioral Adaptations to Social Isolation
Reinsberg, A., Singh, K., Jayaram, M., Mikheim, K., Philips, M., & Vasar, E. (2025) · Brain Sciences · doi:10.3390/brainsci15121286 · Cited by 4
Zhu, B., Li, G., Saunders, J. M., Naler, L. B., Hadlock, T. M., Wang, C., García‐Sastre, A., González‐Maeso, J., & Lu, C. (2026) · Translational Psychiatry · doi:10.1038/s41398-026-03884-z · Cited by 4
Taskiran, S. Y., Taşkıran, M., Ünal, G., Bozkurt, N. M., & Gölgeli, A. (2023) · Behavioural Brain Research · doi:10.1016/j.bbr.2023.114565 · Cited by 2
Herrera, K., Maldonado‐Ruiz, R., Camacho‐Morales, A., de la Garza, A. L., & Castro, H. (2023) · Food & Nutrition Research · doi:10.29219/fnr.v67.9828 · Cited by 3
Kundaković, M. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2016.11.005 · Cited by 2
DNA methylation signatures in autism spectrum disorders
Banerjee, N., & Adak, P. (2021) · The Nucleus · doi:10.1007/s13237-021-00370-3 · Cited by 2
Results and promises of genetics of cognitive impairment in schizophrenia: epigenetic approaches
Алфимова, М. В., Kondratyev, N. V., & Голимбет, В. Е. (2017) · S S Korsakov Journal of Neurology and Psychiatry · doi:10.17116/jnevro201711721130-135 · Cited by 2
Re-evaluating the impact of prenatal low-dose aspirin on child neurodevelopment
Zhu, J., Wang, Y., Liu, Z., & Zhang, J. (2026) · Seminars in Perinatology · doi:10.1016/j.semperi.2026.152256 · Cited by 1
Epigenetics of autism spectrum disorder
Gropman, A. L., & Sadle, C. J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-18516-8.00017-x · Cited by 1
Cytokine Model of Cognition in Relation to Mental Disorders During Neurodevelopment
Fourrier, C., & Baune, B. T. (2020) · Progress in inflammation research · doi:10.1007/978-3-030-39335-9_15 · Cited by 1
DNA methylation and schizophrenia – the role in pathogenesis and the diagnosis of the disease
Płaza, O., & Szulc, A. (2022) · Pharmacotherapy in Psychiatry and Neurology · doi:10.5114/fpn.2022.117702 · Cited by 1
Behavioural effects of cannabidiol in a preclinical model of neurodevelopmental disorders
Alam, T. (2018) · TSpace (University of Toronto)
Saying Something New: The Hidden Patterns in Corpora
Hoey, M. (2005)
(2024) · Cambridge Prisms Precision Medicine · doi:10.1017/pcm.2024.2.pr6
(2024) · Cambridge Prisms Precision Medicine · doi:10.1017/pcm.2024.2.pr5
Khoodoruth, M. A. S. (2024) · Cambridge Prisms Precision Medicine · doi:10.1017/pcm.2024.2.pr4
(2024) · Cambridge Prisms Precision Medicine · doi:10.1017/pcm.2024.2.pr3
(2024) · Cambridge Prisms Precision Medicine · doi:10.1017/pcm.2024.2.pr2
Khoodoruth, M. A. S. (2023) · Cambridge Prisms Precision Medicine · doi:10.1017/pcm.2024.2.pr1
(2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23565-8.09996-8
Anisman, H., Hayley, S. P., & Kusnecov, A. W. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-23565-8.00011-9
Epigenomic alterations in psychiatric disorders and glioblastoma
Šmon, J., Jovčevska, I., Paska, A. V., & Kouter, K. (2025) · Epigenomics · doi:10.1080/17501911.2025.2572960
Huber, A., Vukmirović, J., Haydarlou, R., & Jan Treur, A. (2025) · Cognitive Systems Research · doi:10.1016/j.cogsys.2025.101423
Dong, Y., Weng, J., Zhu, Y., Sun, D., He, W., Chen, Q., Cheng, J., Zhu, Y., & Jiang, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26571244
Dong, Y., Weng, J., Zhu, Y., Sun, D., He, W., Chen, Q., Cheng, J., Zhu, Y., & Jiang, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26571259
Dong, Y., Weng, J., Zhu, Y., Sun, D., He, W., Chen, Q., Cheng, J., Zhu, Y., & Jiang, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26571262
Dong, Y., Weng, J., Zhu, Y., Sun, D., He, W., Chen, Q., Cheng, J., Zhu, Y., & Jiang, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26571274
Dong, Y., Weng, J., Zhu, Y., Sun, D., He, W., Chen, Q., Cheng, J., Zhu, Y., & Jiang, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26571253
Dong, Y., Weng, J., Zhu, Y., Sun, D., He, W., Chen, Q., Cheng, J., Zhu, Y., & Jiang, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26571256
Dong, Y., Weng, J., Zhu, Y., Sun, D., He, W., Chen, Q., Cheng, J., Zhu, Y., & Jiang, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26571247
Dong, Y., Weng, J., Zhu, Y., Sun, D., He, W., Chen, Q., Cheng, J., Zhu, Y., & Jiang, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26571268
Dong, Y., Weng, J., Zhu, Y., Sun, D., He, W., Chen, Q., Cheng, J., Zhu, Y., & Jiang, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26571265
Dong, Y., Weng, J., Zhu, Y., Sun, D., He, W., Chen, Q., Cheng, J., Zhu, Y., & Jiang, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26571250
Dong, Y., Weng, J., Zhu, Y., Sun, D., He, W., Chen, Q., Cheng, J., Zhu, Y., & Jiang, Y. (2024) · Figshare · doi:10.6084/m9.figshare.26571271
Nehme, G., Hendrikse, S. C. F., & Jan Treur, A. (2026) · Studies in computational intelligence · doi:10.1007/978-3-032-13592-6_11
Role of the gut-brain axis in early stress-induced emotional vulnerability
Rincel, M. (2017) · theses.fr (ABES) · doi:10.70675/5e8a972cz9ad1z42aezb89cze6474124ef90
Myelin Matters in Schizophrenia : Neurobiological Insights from Rat Model and Human Studies
Maas, D. A. (2019) · theses.fr (ABES) · doi:10.70675/4ea9aa0azc70cz4bb4zada7z4f82cac02e1c
Carbajal, F. J., LaSalle, J. M., & Bauman, M. D. (2026) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2026.1941243
Metadata
- Authors
- Labouesse, M. A., Dong, E., Grayson, D. R., Guidotti, A., & Meyer, U.
- Affiliations
- ETH Zurich (CH)
- University of Illinois Chicago (US)
- University of Zurich (CH)
- Corresponding author
- Labouesse, Marie Anaïs
- Venue
- Epigenetics
- Publisher
- Informa UK Limited
- Published
- 2015-12-02
- Volume
- 10
- Issue
- 12
- Pages
- 1143-1155
- ISSN
- 1559-2294 (ISSN-L)
- 1559-2308
- PMC
- PMC4844233
- OpenAlex
- W2219458178
- Cited by
- 138
- References
- 87
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 19 · 2023: 11 · 2022: 17 · 2021: 10 · 2020: 13 · 2019: 13 · 2018: 12 · 2017: 14 · 2016: 13
- FWCI
- 5.64
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Epigenetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation (259679)
- European Molecular Biology Organization
- European Commission (FP7/2007-2011, FP7/2007, 259679)
- Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (146217, FP7/2007-2011)
- National Institutes of Health
- U.S. Public Health Service (NIMH2013-00362)
- National Institute of Mental Health (R01MH093348)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- maternal immune activation, prenatal infection, poly(I:C), GAD1, GAD-2, glutamic acid decarboxylase, GABA synthesis, prefrontal cortex, DNA methylation, 5-hydroxymethylcytosine, MeCP2, epigenetic regulation, working memory, social interaction, neurodevelopmental disorders, childhood adversity
- MeSH terms
- Animals, Binding Sites, Female, Glutamate Decarboxylase, Immunity, Innate, Pregnancy, Prenatal Exposure Delayed Effects, Promoter Regions, Genetic, RNA, Messenger, Prefrontal Cortex, DNA Methylation, Epigenesis, Genetic, Mice, Methyl-CpG-Binding Protein 2
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
