Related Experiment Video
Updated: Aug 17, 2026
Developing a Behavioral Box for Assessing Prepulse Inhibition and Neural Activity in Psychiatric Animal Models
Published on: July 22, 2025
Towards an immuno-precipitated neurodevelopmental animal model of schizophrenia
Urs Meyer1, Joram Feldon, Manfred Schedlowski
1Laboratory of Behavioural Neurobiology, Swiss Federal Institute of Technology Zurich, Schorenstrasse 16, Schwerzenbach 8603, Switzerland.
Insights
Maternal infections during pregnancy may increase schizophrenia risk in offspring. Prenatal exposure to polyriboinosinic-polyribocytidilic acid (PolyI:C) in mice induced schizophrenia-related behavioral deficits, modeling this link.
Area of Science:
- Neuroscience
- Immunology
- Psychiatry
Background:
- Epidemiological studies link maternal infections during pregnancy to increased schizophrenia risk in offspring.
- A leading hypothesis suggests prenatal immune activation via maternal cytokines mediates this association.
Purpose of the Study:
- To investigate if prenatal exposure to a cytokine-releasing agent, polyriboinosinic-polyribocytidilic acid (PolyI:C), can induce schizophrenia-related behavioral deficits in adult mice.
- To establish PolyI:C administration as a relevant animal model for studying schizophrenia's developmental etiology.
Main Methods:
- Pregnant mice were injected with PolyI:C (2.5, 5.0, or 10.0 mg/kg) or vehicle on gestation day 9.
- Cytokine levels (interleukin-10, interleukin-1beta) were measured in adult females and fetal brain tissue post-PolyI:C exposure.
- Offspring behavior was assessed in adulthood for deficits including exploratory behavior, prepulse inhibition, memory, and amphetamine response.
Main Results:
- Prenatal PolyI:C exposure resulted in offspring exhibiting multiple schizophrenia-related behavioral deficits.
- PolyI:C administration induced dose-dependent elevations in interleukin-10 in adult females and interleukin-1beta in fetal brain tissue.
- Observed deficits included impaired cognitive functions and altered responses to amphetamine and learning tasks.
Conclusions:
- Prenatal PolyI:C exposure in mice provides a robust environmental-developmental model for schizophrenia.
- This model demonstrates epidemiological and immunological relevance, suitable for investigating neuropsychoimmunological mechanisms in schizophrenia development.
- The findings support the hypothesis that prenatal immune activation contributes to schizophrenia etiology.
Abstract:
Epidemiological studies have indicated an association between maternal bacterial and viral infections during pregnancy and the higher incidence of schizophrenia in the resultant offspring post-puberty. One hypothesis asserts that the reported epidemiological link is mediated by prenatal activation of the foetal immune system in response to the elevation of maternal cytokine level due to infection. Here, we report that pregnant mouse dams receiving a single exposure to the cytokine-releasing agent, polyriboinosinic-polyribocytidilic acid (PolyI:C; at 2.5, 5.0, or 10.0 mg/kg) on gestation day 9 produced offspring that subsequently exhibited multiple schizophrenia-related behavioural deficits in adulthood, in comparison to offspring from vehicle injected or non-injected control dams. The efficacy of the PolyI:C challenge to induce cytokine responses in naïve non-pregnant adult female mice and in foetal brain tissue when injected to pregnant mice were further ascertained in separate subjects: (i) a dose-dependent elevation of interleukin-10 was detected in the adult female mice at 1 and 6h post-injection, (ii) 12 h following prenatal PolyI:C challenge, the foetal levels of interleukin-1beta were elevated. The spectrum of abnormalities included impairments in exploratory behaviour, prepulse inhibition, latent inhibition, the US-pre-exposure effect, spatial working memory; and enhancement in the locomotor response to systemic amphetamine (2.5 mg/kg, i.p.) as well as in discrimination reversal learning. The neuropsychological parallels between prenatal PolyI:C treatment in mice and psychosis in humans, demonstrated here, leads us to conclude that prenatal PolyI:C treatment represents one of the most powerful environmental-developmental models of schizophrenia to date. The uniqueness of this model lies in its epidemiological and immunological relevance. It is, sui generis, ideally suited for the investigation of the neuropsychoimmunological mechanisms implicated in the developmental aetiology and disease processes of schizophrenia.
