Immune activation during pregnancy in mice leads to dopaminergic hyperfunction and cognitive impairment in the offspring: a neurodevelopmental animal model of schizophrenia
Abstract
Background Maternal viral infection is associated with increased risk for schizophrenia. It is hypothesized that the maternal immune response to viruses may influence fetal brain development and lead to schizophrenia.Methods To mimic a viral infection, the synthetic double strand RNA polyriboinosinic-polyribocytidilic acid (poly I:C) was administered into pregnant mice. Behavioral evaluations (thigmotaxis, methamphetamine [MAP]-induced hyperactivity, novel-object recognition test [NORT]), sensorimotor gating (prepulse inhibition [PPI]), and biochemical evaluation of the dopaminergic function of the offspring of phosphate-buffered saline (PBS)-treated dams (PBS-mice) and that of poly I:C-treated dams (poly I:C-mice) were examined.Results In juveniles, no difference was found between the poly I:C-mice and PBS-mice. However, in adults, the poly I:C-mice exhibited attenuated thigmotaxis, greater response in MAP-induced (2 mg/kg) hyperlocomotion, deficits in PPI, and cognitive impairment in NORT compared with the PBS-mice. Cognitive impairment in the adult poly I:C-mice could be improved by subchronic administration of clozapine (5.0 mg/kg) but not haloperidol (.1 mg/kg). Increased dopamine (DA) turnover and decreased receptor binding of D2-like receptors, but not D1-like receptors, in the striatum were found in adult poly I:C-mice.Conclusions Prenatal poly I:C administration causes maturation-dependent increased subcortical DA function and cognitive impairment in the offspring, indicating a neurodevelopmental animal model of schizophrenia.
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Prenatal poly(I:C) exposure impaired novel object recognition performance.
“performance in the novel object recognition task (Ozawa et al., 2006)”
From Neuroinflammation as a risk factor for attention deficit hyperactivity disorder (2019) · cites this paper as Ozawa et al., 2006
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- Authors
- Ozawa, K., Hashimoto, K., Kishimoto, T., Shimizu, E., Ishikura, H., & Iyo, M.
- Affiliations
- Chiba University (JP)
- Corresponding author
- Ozawa, Kimiyoshi
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 59
- Issue
- 6
- Pages
- 546-554
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2031337229
- Cited by
- 467
- References
- 64
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 18 · 2023: 13 · 2022: 30 · 2021: 19 · 2020: 19 · 2019: 21 · 2018: 29 · 2017: 11 · 2016: 24 · 2015: 31 · 2014: 28 · 2013: 25 · 2012: 29
- FWCI
- 6.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Maternal Mental Health During Pregnancy and Postpartum
- Keywords
- maternal immune activation, poly(I:C), prenatal viral infection, schizophrenia, cognitive impairment, prepulse inhibition, novel object recognition, clozapine, D2-like receptors, dopamine turnover, striatum, thigmotaxis
- MeSH terms
- Animals, Animals, Newborn, Antibodies, Viral, Brain, Clozapine, Cognition, Disease Models, Animal, Exploratory Behavior, Female, Form Perception, Methamphetamine, Mice, Inbred BALB C, Motor Activity, Neural Inhibition, Orientation, Poly I-C, Pregnancy, Pregnancy Complications, Infectious, Pregnancy, Animal, Prenatal Exposure Delayed Effects, Mental Recall, Schizophrenia, Reflex, Startle, Virus Diseases, Neuroimmunomodulation, Cytokines, Mice
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 ›
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