Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after in utero immune challenge
Relative prenatal and postnatal maternal contributions to schizophrenia-related neurochemical dysfunction after in utero immune challenge
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DOI：
10.1038/sj.npp.1301413
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发表时间：
2008-01-01
影响因子：
7.6
通讯作者：
Feldon, Joram
中科院分区：
文献类型：
--
作者：
Meyer, Urs;Nyffeler, Myriel;Feldon, Joram
产前接触感染是晚年出现神经精神疾病（包括精神分裂症和自闭症）的危险因素。然而，目前尚不清楚这种关联是否主要归因于产前和/或产后母亲对后代的影响。在这里，我们通过剖析产前病毒样感染动物模型中产前炎症事件和产后母体因素的相对贡献来解决这个问题。怀孕小鼠在妊娠第 9 天接受炎症剂聚核糖肌苷-聚核糖胞二酸（Polyl:C；5 mg/kg，静脉注射）或媒介物治疗，Polyl:C 和媒介物处理的母鼠所生的后代与在怀孕期间经历过炎症或假治疗的代孕母亲交叉抚养。我们证明，无论新生儿是由暴露于媒介物还是 Polyl:C 的代孕母亲抚养，在产前免疫攻击后都会出现多种与多巴胺和谷氨酸相关的药理学和神经解剖学紊乱。然而，将产前对照动物收养给免疫缺陷的代孕母亲也足以在养育的后代中诱导特定的药理学和神经解剖学异常。因此，产前免疫挑战后出现的多种精神分裂症相关功能障碍是由产前而非产后母体对后代的影响介导的，但怀孕期间的免疫应激可能会影响产后母体因素，从而使由免疫缺陷的代孕母亲抚养长大可能会在成年生活中带来不同形式的精神病理学风险。
Prenatal exposure to infections represents a risk factor for the emergence of neuropsychiatric disorders in later life, including schizophrenia and autism. However, it remains essentially unknown whether this association is primarily attributable to prenatal and/or postnatal maternal effects on the offspring. Here, we addressed this issue by dissecting the relative contributions of prenatal inflammatory events and postnatal maternal factors in an animal model of prenatal viral-like infection. Pregnant mice were exposed to the inflammatory agent polyriboinosinic-polyribocytidilic acid (Polyl:C; 5 mg/kg, i.v.) or vehicle treatment on gestation day 9, and offspring born to Polyl:C-and vehicle-treated dams were cross fostered to surrogate rearing mothers that had either experienced inflammatory or sham treatment during pregnancy. We demonstrate that a variety of dopamine- and glutamate-related pharmacological and neuroanatomical disturbances emerge after prenatal immune challenge regardless of whether neonates were raised by vehicle- or Polyl:C-exposed surrogate mothers. However, the adoption of prenatal control animals to immune-challenged surrogate mothers was also sufficient to induce specific pharmacological and neuroanatomical abnormalities in the fostered offspring. Multiple schizophrenia-related dysfunctions emerging after prenatal immune challenge are thus mediated by prenatal but not postnatal maternal effects on the offspring, but immunological stress during pregnancy may affect postpartum maternal factors in such a way that being reared by an immune-challenged surrogate mother can confer risk for distinct forms of psychopathology in adult life.