Prenatal stress induces schizophrenia-like alterations of serotonin 2A and metabotropic glutamate 2 receptors in the adult offspring: role of maternal immune system.
Prenatal stress induces schizophrenia-like alterations of serotonin 2A and metabotropic glutamate 2 receptors in the adult offspring: role of maternal immune system.
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DOI：
10.1523/jneurosci.2331-12.2013
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发表时间：
2013-01-16
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影响因子：
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通讯作者：
González-Maeso J
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文献类型：
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作者：
Holloway T;Moreno JL;Umali A;Rayannavar V;Hodes GE;Russo SJ;González-Maeso J
有研究表明，怀孕期间发生的严重不良生活事件会增加后代患精神分裂症的风险。5-羟色胺5-HT 2A和代谢型谷氨酸2（mGlu 2）受体都是精神分裂症和抗精神病药物开发方面相当关注的目标。我们测试了怀孕期间母体可变应激对小鼠这两种受体表达和行为功能的影响。产前应激增加5-HT 2A和减少mGlu 2在额叶皮层，大脑区域参与感知，认知和情绪的表达。5-HT 2A和mGlu 2受体的这种表达模式与行为改变一致，包括对致幻5-HT 2A激动剂DOI的头部抽搐反应增加，以及mGlu 2/3激动剂LY 379268在成年但非青春期前的小鼠中的mGlu 2依赖性抗精神病样作用降低，这些小鼠是在妊娠期间由压力母亲所生的。交叉培养研究确定，这些变化不是由于产前压力对产妇护理的影响。此外，在妊娠期间注射poly-（I：C）的母亲所生的小鼠中观察到类似的生化和行为变化模式，作为产前免疫激活的模型。这些数据加强了病理生理学假说，提出了精神分裂症和其他精神疾病的早期神经发育起源。
It has been suggested that severe adverse life events during pregnancy increase the risk of schizophrenia in the offspring. The serotonin 5-HT2A 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-HT2A and decreased mGlu2 expression in frontal cortex, a brain region involved in perception, cognition and mood. This pattern of expression of 5-HT2A and mGlu2 receptors was consistent with behavioral alterations, including increased head-twitch response to the hallucinogenic 5-HT2A agonist DOI, and decreased mGlu2-dependent antipsychotic-like effect of the mGlu2/3 agonist LY379268 in adult, but not prepubertal, mice born to stressed mothers during pregnancy. Cross-fostering studies determined that these alterations were not due 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 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.