Late Prenatal Immune Activation in Mice Leads to Behavioral and Neurochemical Abnormalities Relevant to the Negative Symptoms of Schizophrenia
| Autor: | Joram Feldon, Urs Meyer, Daria Peleg-Raibstein, Byron K.Y. Bitanihirwe, Forouhar Mouttet |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Psychosis Offspring Dopamine Glycine Glutamic Acid Prefrontal Cortex Physiology Hippocampus Mice Neurochemical Latent inhibition Pregnancy medicine Animals Prefrontal cortex gamma-Aminobutyric Acid Pharmacology Sex Characteristics Behavior Animal Anhedonia medicine.disease Mice Inbred C57BL Disease Models Animal Psychiatry and Mental health Poly I-C Schizophrenia Prenatal Exposure Delayed Effects Central Nervous System Viral Diseases Female Schizophrenic Psychology Original Article medicine.symptom Psychology Neuroscience |
| Zdroj: | Neuropsychopharmacology. 35:2462-2478 |
| ISSN: | 1740-634X 0893-133X |
| Popis: | Based on the human epidemiological association between prenatal infection and higher risk of schizophrenia, a number of animal models have been established to explore the long-term brain and behavioral consequences of prenatal immune challenge. Accumulating evidence suggests that the vulnerability to specific forms of schizophrenia-related abnormalities is critically influenced by the precise timing of the prenatal immunological insult. In the present study, we tested the hypothesis whether late prenatal immune challenge in mice may induce long-term behavioral and neurochemical dysfunctions primarily associated with the negative symptoms of schizophrenia. We found that prenatal exposure to the viral mimic polyriboinosinic-polyribocytidilic acid (Poly-I:C; 5 mg/kg, i.v.) on gestation day (GD) 17 led to significant deficits in social interaction, anhedonic behavior, and alterations in the locomotor and stereotyped behavioral responses to acute apomorphine (APO) treatment in both male and female offspring. In addition, male but not female offspring born to immune challenged mothers displayed behavioral/cognitive inflexibility as indexed by the presence of an abnormally enhanced latent inhibition (LI) effect. Prenatal immune activation in late gestation also led to numerous, partly sex-specific changes in basal neurotransmitter levels, including reduced dopamine (DA) and glutamate contents in the prefrontal cortex and hippocampus, as well as reduced γ-aminobutyric acid (GABA) and glycine contents in the hippocampus and prefrontal cortex, respectively. The constellation of behavioral and neurochemical abnormalities emerging after late prenatal Poly-I:C exposure in mice leads us to conclude that this immune-based experimental model provides a powerful neurodevelopmental animal model especially for (but not limited to) the negative symptoms of schizophrenia. |
| Databáze: | OpenAIRE |
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