Prenatal Stress Induces Schizophrenia-Like Alterations of Serotonin 2A and Metabotropic Glutamate 2 Receptors in the Adult Offspring: Role of Maternal Immune System
Terrell Holloway, José L. Moreno, Adrienne Umali, Vinayak Rayannavar, Georgia E. Hodes, Scott J. Russo, Javier González‐maeso
Journal of Neuroscience January 16, 2013 DOI: 10.1523/jneurosci.2331-12.2013 via OpenAlex
Summary
Severe stress during pregnancy in mice alters the expression of two brain receptors linked to schizophrenia: serotonin 5-HT2A increases and metabotropic glutamate mGlu2 decreases in the frontal cortex. These changes correspond to behavioral differences in adult offspring, such as a heightened response to a hallucinogenic drug and reduced antipsychotic-like effects of a mGlu2/3 agonist. Cross-fostering ruled out maternal care as a cause, and similar effects appeared after prenatal immune activation. The findings support the idea that early neurodevelopmental disruptions contribute to schizophrenia risk.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice |
| Topics | Serotonin |
| Keywords | Offspring Metabotropic receptor Metabotropic glutamate receptor Psychology Pregnancy |
| Citations | 122 |
| Key finding | Prenatal stress increased 5-HT2A and decreased mGlu2 receptor expression in the frontal cortex, with corresponding behavioral changes in adult but not prepubertal mice. |
Abstract
It has been suggested that severe adverse life events during pregnancy increase the risk of schizophrenia in the offspring. The serotonin 5-HT 2A and the metabotropic glutamate 2 (mGlu2) receptors both have been the target of considerable attention regarding schizophrenia and antipsychotic drug development. We tested the effects of maternal variable stress during pregnancy on expression and behavioral function of these two receptors in mice. Prenatal stress increased 5-HT 2A and decreased mGlu2 expression in frontal cortex, a brain region involved in perception, cognition, and mood. This pattern of expression of 5-HT 2A and mGlu2 receptors was consistent with behavioral alterations, including increased head-twitch response to the hallucinogenic 5-HT 2A agonist DOI [1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane] and decreased mGlu2-dependent antipsychotic-like effect of the mGlu2/3 agonist LY379268 (1 R ,4 R ,5 S ,6 R -2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate) in adult, but not prepubertal, mice born to stressed mothers during pregnancy. Cross-fostering studies determined that these alterations were not attributable to effects of prenatal stress on maternal care. Additionally, a similar pattern of biochemical and behavioral changes were observed in mice born to mothers injected with polyinosinic:polycytidylic acid [poly(I:C)] during pregnancy as a model of prenatal immune activation. These data strengthen pathophysiological hypotheses that propose an early neurodevelopmental origin for schizophrenia and other psychiatric disorders.