The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.
Combined effect of neonatal immune activation and mutant DISC1 on phenotypic changes in adulthood
Open accessAbstract
Gene-environment interaction may play a role in the etiology of schizophrenia. Transgenic mice expressing dominant-negative DISC1 (DN-DISC1 mice) show some histological and behavioral endophenotypes relevant to schizophrenia. Viral infection during neurodevelopment provides a major environmental risk for schizophrenia. Neonatal injection of polyriboinosinic-polyribocytidylic acid (polyI:C), which mimics innate immune responses elicited by viral infection, leads to schizophrenia-like behavioral alteration in mice after puberty. To study how gene-environmental interaction during neurodevelopment results in phenotypic changes in adulthood, we treated DN-DISC1 mice or wild-type littermates with injection of polyI:C during the neonatal stage, according to the published method, respectively, and the behavioral and histological phenotypes were examined in adulthood. We demonstrated that neonatal polyI:C treatment in DN-DISC1 mice resulted in the deficits of short-term, object recognition, and hippocampus-dependent fear memories after puberty, although polyI:C treatment by itself had smaller influences on wild-type mice. Furthermore, polyI:C-treated DN-DISC1 mice exhibited signs of impairment of social recognition and interaction, and augmented susceptibility to MK-801-induced hyperactivity as compared with vehicle-treated wild-type mice. Of most importance, additive effects of polyI:C and DN-DISC1 were observed by a marked decrease in parvalbumin-positive interneurons in the medial prefrontal cortex. These results suggest that combined effect of neonatal polyI:C treatment and DN-DISC1 affects some behavioral and histological phenotypes in adulthood.
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
“Activated innate immune cells both produce and are activated by ROS: antioxidant therapy with NAC reduces the pathological and behavioural consequences of maternal LPS treatment and reduces foetal proinflammatory cytokine production 92,93 .”
From Linking early-life NMDAR hypofunction and oxidative stress in schizophrenia pathogenesis (2016) · 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
The Mouse Brain in Stereotaxic Coordinates
Paxinos, G. (2001) · Cited by 12,859
Gerdes, J., Lemke, H., Baisch, H., Wacker, H. H., Schwab, U., & Stein, H. (1984) · The Journal of Immunology · doi:10.4049/jimmunol.133.4.1710 · Cited by 4,173 · cited 1×
“We conducted Nissl-staining, BrdU staining, and immunohistochemistry for Ki67 (a marker of cell proliferation) [2,8].”
MethodCortical inhibitory neurons and schizophrenia
Lewis, D. A., Hashimoto, T., & Volk, D. W. (2005) · Nature Reviews Neuroscience · doi:10.1038/nrn1648 · Cited by 2,297 · cited 3×
“Of note, as far as we are aware, this is the first experimental demonstration that “neonatal” interaction of major genetic and environmental susceptibility factors for schizophrenia results in the dramatic change in the parvalbumin-positive interneurons in the medial prefrontal cortex (mPFC), one of the best hallmarks…”
BackgroundSchizophrenia genes, gene expression, and neuropathology: on the matter of their convergence
Harrison, P. J., & Weinberger, D. R. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001558 · Cited by 2,020
Neuregulin 1 and Susceptibility to Schizophrenia
Stefánsson, H., Pétursson, H., Sigurðsson, E., Steinthórsdóttir, V., Bjornsdottir, S., Sigmundsson, T., Ghosh, S., Brynjolfsson, J., Gunnarsdottir, S., Ivarsson, O., et al. (2002) · The American Journal of Human Genetics · doi:10.1086/342734 · Cited by 1,671 · cited 1×
“For the past a couple of years, many lines of genetic mouse models based on susceptibility genes for schizophrenia have become available and characterized mainly by behavioral alterations [10,13,18,19,25].”
BackgroundMaternal 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 1×
“PolyI:C is a toll-like receptor 3 ligand that induces a strong innate immune response, and has been used to mimic viral infection during neurodevelopment [15,23].”
BackgroundGene–environment interactions in psychiatry: joining forces with neuroscience
Caspi, A., & Moffitt, T. E. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1925 · Cited by 1,300 · cited 1×
“Furthermore, the possible interaction between environmental and genetic susceptibility factors, especially during neurodevelopment, is proposed as a promising disease etiology of schizophrenia [5,14].”
BackgroundLisman, J. E., Coyle, J. T., Green, R. W., Javitt, D. C., Benes, F. M., Heckers, S., & Grace, A. A. (2008) · Trends in Neurosciences · doi:10.1016/j.tins.2008.02.005 · Cited by 1,010 · cited 2×
“Of note, as far as we are aware, this is the first experimental demonstration that “neonatal” interaction of major genetic and environmental susceptibility factors for schizophrenia results in the dramatic change in the parvalbumin-positive interneurons in the medial prefrontal cortex (mPFC), one of the best hallmarks…”
BackgroundThe Neurodevelopmental Hypothesis of Schizophrenia, Revisited
Fatemi, S. H., & Folsom, T. D. (2009) · Schizophrenia Bulletin · doi:10.1093/schbul/sbn187 · Cited by 860 · cited 1×
“Accordingly, it is possible that the changes in PPI response in DN-DISC1 mice may be undetectable at younger ages as we selected [24].”
BackgroundMeyer, U., Nyffeler, M., Engler, A., Urwyler, A., Schedlowski, M., Knuesel, I., Yee, B. K., & Feldon, J. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0099-06.2006 · Cited by 774 · cited 1×
“PolyI:C is a toll-like receptor 3 ligand that induces a strong innate immune response, and has been used to mimic viral infection during neurodevelopment [15,23].”
Background
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–137 of 137
Interaction of DISC1 with the PTB domain of Tensin2
Goudarzi, S., Smith, L., Schütz, S., & Hafizi, S. (2012) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-012-1228-6 · Cited by 11
“However, it is most likely that the fullest expression of the disease arises from the combined effects of both genetic and environmental factors that contribute to the neurodevelopmental model of schizophrenia [2].”
Effects of sub-acute and sub-chronic inhalation of 1-bromopropane on neurogenesis in adult rats
Zhang, L., Nagai, T., Yamada, K., Ibi, D., Ichihara, S., Subramanian, K., Huang, Z., Mohideen, S. S., Naito, H., & Ichihara, G. (2012) · Toxicology · doi:10.1016/j.tox.2012.12.009 · Cited by 11
Self-citationPharmacological and proteomic analyses of neonatal polyI:C-treated adult mice
Kitagawa, K., Nagai, T., & Yamada, K. (2018) · Neuroscience Research · doi:10.1016/j.neures.2018.10.007 · Cited by 10
Self-citationDeng, D., Jian, C., Lei, L., Zhou, Y., McSweeney, C., Dong, F., Shen, Y., Zou, D., Wang, Y., Wu, Y., et al. (2017) · Oncotarget · doi:10.18632/oncotarget.21381 · Cited by 9
“Moreover, our results together with other studies [72] suggest that the interaction of genetic risks with environmental triggers may be needed to elicit more severe psychiatric symptoms.”
ResultSusceptibility Genes for Schizophrenia: Mutant Models, Endophenotypes and Psychobiology
O’Tuathaigh, C. M. P., Desbonnet, L., Moran, P. M., & Waddington, J. L. (2011) · Current topics in behavioral neurosciences · doi:10.1007/7854_2011_194 · Cited by 8
Yu, J. (2010) · The Open Behavioral Science Journal · doi:10.2174/1874230001004010009 · Cited by 6
Kelly, M. P., & Brandon, N. (2011) · Future Neurology · doi:10.2217/fnl.11.39 · Cited by 15
“CAMKIIa-regulated transgenic expression of truncated hDisc1 ↔ Increased sensitivity to poly(I:C) immune challenge [12,13]”
BackgroundInfluentialLahogue, C., Boulouard, M., Menager, F., Fréret, T., Billard, J., & Bouët, V. (2024) · Behavioural Brain Research · doi:10.1016/j.bbr.2024.115301 · Cited by 6
“This behavioral signature is also found in mice with genetic deletion of the Disrupted in schizophrenia 1 gene (DISC1) [61-63], one of the genes recognized to be associated with SCZ [64], notably due to its implication in glutamatergic neurotransmission and in the stabilization of SR [25, 63].”
BackgroundNeuroplasticity Across the Autism–Schizophrenia Continuum
Kesidou, E., Mitsoudis, N., Damianidou, O., Taloumtzis, C., Tsakiridou, M., Polyzoidou, E., Grigoriadou, E., Bakirtzis, C., Spandou, E., & Simeonidou, C. (2025) · Biomedicines · doi:10.3390/biomedicines13112695 · Cited by 5
“Another crucial fact about DISC1 is that postnatally, it regulates the maturation of dopaminergic and GABAergic synaptic transmission, especially in the prefrontal cortex and that the modification of the gene at specific time points has shown to alter this maturation [75].”
Scott, D. E., & Tamminga, C. A. (2017) · Behavioural Brain Research · doi:10.1016/j.bbr.2017.10.039 · Cited by 5
Twinfilin-1 phosphorylation in reelin signaling regulates actin dynamics and spine development
Dong, G., Mori, D., Matsuzaki, T., Tanaka, R., Itoh, N., Matsui, T., Sato, A., Arioka, Y., Okumura, H., Fukaya, R., et al. (2025) · Pharmacological Research · doi:10.1016/j.phrs.2025.107986 · Cited by 4
Self-citationLi, S., Zheng, Y., Li, X., Lan, S., Xiang, J., Liao, L., Lin, Y., & Ye, Y. (2022) · Behavioural Pharmacology · doi:10.1097/fbp.0000000000000702 · Cited by 4
“The alternation percentage was obtained as the ratio of actual to possible alternations (expressed as the overall number of arm entries minus two) multiplied by 100 (Ibi et al., 2010).”
MethodYu, J., Nagai, T., Ibi, D., Kitahara, Y., Nabeshima, T., & Yamada, K. (2010) · The Open Behavioral Science Journal · Cited by 4
Self-citationModeling Gene–Environment Interaction in Schizophrenia
Jouroukhin, Y., McFarland, R., Ayhan, Y., & Pletnikov, M. V. (2015) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-12-800981-9.00020-1 · Cited by 3
Genetic animal models for psychiatric disorders
Zhou, Y., Samsom, J., & Wong, A. H. C. (2022) · Elsevier eBooks · doi:10.1016/b978-0-12-819602-1.00015-2 · Cited by 4
Delevich, K. M., Jaaro-Peled, H., Penzo, M. A., Sawa, A., & Li, B. (2016) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/054759 · Cited by 2
“Furthermore, a variety of DISC1 mouse models also exhibit reduced prefrontal PV expression (Ayhan et al., 2011; Hikida et al., 2007; Ibi et al., 2010; Lee et al., 2013; Niwa et al., 2010; Shen et al., 2008), suggesting that PV INs may be particularly affected by DISC1 perturbation.”
BackgroundSelf-citationVolgin, A. D., Cheresiz, S. V., Chizhova, N. D., Smirnova, K. V., Doroshkov, A. V., Galstya, D. S., de Abreu, M. S., Strekalova, T. V., Lipina, T. V., Pletnikov, M. V., et al. (2025) · Journal of Integrative Neuroscience · doi:10.31083/jin43162 · Cited by 1
“Introduction of DN-Disc1 mice to PolyI:C daily during embryonic development, impairs short-term memory in the object recognition task and contextual fear memory [132].”
Managò, F., Huang, H., & Papaleo, F. (2015) · Handbook of behavioral neuroscience · doi:10.1016/b978-0-12-800981-9.00006-7 · Cited by 1
Ellenbroek, B. A., & Youn, J. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-801657-2.00009-4 · Cited by 1
Neural Circuits and Some New Factors Involved in Hippocampal Memory
Jing, R., Cai, Q., Li, W., & Zhang, X. (2022) · IntechOpen eBooks · doi:10.5772/intechopen.101309 · Cited by 2
Park, J., Shimbo, H., Tamura, S., Tomoda, T., Hikida, T., Okado, H., & Hirai, S. (2024) · Behavioural Brain Research · doi:10.1016/j.bbr.2024.115291 · Cited by 1
Deane, A. R., & Ward, R. D. (2022) · Journal of the Experimental Analysis of Behavior · doi:10.1002/jeab.753 · Cited by 2
Evaluation of novel dual-hit models of 'schizophrenia-like' symptoms in the rat
Gaskin, P. L. R. (2014) · UPT. Syiah Kuala University Library (Syiah Kuala University)
Plana, G. A. (2014) · Repositori digital de la UPF (Universitat Pompeu Fabra)
Disrupted-in-Schizophrenia-1 (DISC1) Interactome and Schizophrenia
Lipina, T. V., & Roder, J. (2015) · Royal Society of Chemistry eBooks · doi:10.1039/9781782622499-00141
Oskvig, D. B. (2010) · DigitalGeorgetown (Georgetown University Library)
Phenotypic characterization of C57BL/6J mice carrying the Disc1 gene from the 129S6/SvEv strain
Lee, J., & Hwu, G. (2014)
Depoortère, R., & Moser, P. C. (2014) · Methods and principles in medicinal chemistry · doi:10.1002/9783527679348.ch10
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
Port, J. D. (2024) · Journal of Magnetic Resonance Imaging · doi:10.1002/jmri.29644
“One such model is the lactational polyriboinosinic-polyribocytidilic acid (Poly I:C) rat model 4,5 where female rats are administered Poly I:C shortly after delivering their litters.”
Amestoy, A., Mallet, J., Iftimovici, A., Lefebvre, A., & Stéphan, F. (2025) · médecine/sciences · doi:10.1051/medsci/2025070
Neurodevelopmental impairment following neonatal immune challenge in mice
Yamada, K. (2013) · Folia Pharmacologica Japonica · doi:10.1254/fpj.142.221
Dual Stress Postischemia Deprivation Depression via Metabolic Disturbance in Rodents
Fan, R., Lu, R., Liu, Y., Hou, B., Li, Z., Xie, J., Zhang, R., & Zhou, N. (2026) · Journal of Surgical Research · doi:10.1016/j.jss.2026.01.015
The Impact of Oxidative Stress on GAD67 Levels and Parvalbumin-Positive Neurons
Deslauriers, J., & Grignon, S. (2014) · Oxidative stress in applied basic research and clinical practice · doi:10.1007/978-1-4939-0440-2_22
Metadata
- Authors
- Ibi, D., Nagai, T., Koike, H., Kitahara, Y., Mizoguchi, H., Niwa, M., Jaaro-Peled, H., Nitta, A., Yoneda, Y., & Nabeshima, T.
- Affiliations
- Nagoya University Hospital (JP)
- Nagoya University (JP)
- Kanazawa University (JP)
- Research Institute of Environmental Medicine, Nagoya University (JP)
- Johns Hopkins University (US)
- Meijo University (JP)
- ORCID
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2010-01-05
- Volume
- 206
- Issue
- 1
- Pages
- 32-37
- ISSN
- 0166-4328 (ISSN-L)
- PMC
- PMC2846597
- OpenAlex
- W1988682809
- Cited by
- 137
- References
- 26
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 3 · 2023: 1 · 2022: 5 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 10 · 2017: 12 · 2016: 9 · 2015: 15 · 2014: 12 · 2013: 17 · 2012: 11
- FWCI
- 7.42
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (P20MH084018, R01MH069853)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- schizophrenia, gene-environment interaction, DISC1, poly(I:C), viral infection, brain development, object recognition, social recognition, fear memory, hippocampus, parvalbumin interneurons, medial prefrontal cortex, transgenic mice
- MeSH terms
- Analysis of Variance, Animals, Animals, Newborn, Behavior, Animal, Conditioning, Classical, Fear, Female, Hippocampus, Hyperkinesis, Immunohistochemistry, Interferon Inducers, Male, Memory, Short-Term, Mice, Transgenic, Nerve Tissue Proteins, Parvalbumins, Phenotype, Poly I-C, Social Behavior, Staining and Labeling, Reflex, Startle, Dizocilpine Maleate, Ki-67 Antigen, Recognition, Psychology, Freezing Reaction, Cataleptic, Cell Proliferation, Mice, Sensory Gating
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
