To poly(I:C) or not to poly(I:C): Advancing preclinical schizophrenia research through the use of prenatal immune activation models

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Abstract

The neurodevelopmental hypothesis of schizophrenia has been highly influential in shaping our current thinking about modeling the disease in animals. Based on the findings provided by human epidemiological studies, a great deal of recent interest has been centered upon the establishment of neurodevelopmental rodent models in which the basic experimental manipulation takes the form of prenatal exposure to infection and/or immune activation. One such model is based on prenatal treatment with the inflammatory agent poly(I:C) (=polyriboinosinic-polyribocytidilic acid), a synthetic analog of double-stranded RNA. Since its initial establishment and application to basic schizophrenia research, the poly(I:C) model has made a great impact on researchers concentrating on the neurodevelopmental and neuroimmunological basis of complex human brain disorders such as schizophrenia, and as a consequence, the model now enjoys wide recognition in the international scientific community. The present article emphasizes that the poly(I:C) model has gained such impact because it successfully accounts for several aspects of schizophrenia epidemiology, pathophysiology, symptomatology, and treatment. The numerous features of this experimental system make the poly(I:C) model a very powerful neurodevelopmental animal model of schizophrenia-relevant brain disease which is expected to be capable of critically advancing our knowledge of how the brain, following an (immune-associated) triggering event in early life, can develop into a “schizophrenia-like brain” over time. Furthermore, the poly(I:C) model seems highly suitable for the exploration of novel pharmacological and neuro-immunomodulatory strategies for both symptomatic and preventive treatments against psychotic disease, as well as for the identification of neurobiological mechanisms underlying gene–environment and environment–environment interactions presumably involved in the etiology of schizophrenia and related disorders.

This article is part of a Special Issue entitled ‘Schizophrenia’.

Highlights

▸ The prenatal poly(I:C) model is one of the currently available immune activation models in rodents. ▸ The model mimics multiple brain and behavioral abnormalities implicated in schizophrenia. ▸ The model may help to improve symptomatic and preventive interventions for schizophrenic disease.

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