Prenatal immune activation induces age-related alterations in rat offspring: Effects upon NMDA receptors and behaviors
Prenatal immune activation induces age-related alterations in rat offspring: Effects upon NMDA receptors and behaviors
复制标题
产前免疫激活诱导大鼠后代发生与年龄相关的改变：对 NMDA 受体和行为的影响
DOI：
10.1016/j.bbr.2019.111946
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发表时间：
2019-09-16
影响因子：
2.7
通讯作者：
Lv, Luxian
中科院分区：
文献类型：
--
作者：
Hao, Keke;Su, Xi;Lv, Luxian
产前暴露于多聚核糖肌苷酸多聚核糖胞苷酸（poly I：C）导致成熟大鼠后代出现精神病样行为，以及对神经元兴奋性突触传递的持久修饰。然而，鲜为人知的是动态行为和谷氨酸N-甲基-D-天冬氨酸（NMDA）受体的变化，大鼠后代聚I：C治疗怀孕的母鼠。在本研究中，在妊娠第9天以10 mg/kg的剂量对大鼠静脉给予聚I：C，以评估后代行为和NMDA受体随时间的变化。结果表明，青少年和成人的行为进行性恶化，表现为焦虑增加，认知障碍和前脉冲抑制缺陷。从断奶到成年，观察到前额叶皮层和海马中NMDA受体的数量和分布的变化。这些结果表明，NMDA受体的异常发生在明显的精神分裂症样行为表现之前。因此，NMDA受体可能是潜在的治疗目标，以防止疾病的发展，在无症状期的精神分裂症，并可能作为目标的预防和/或治疗策略，精神分裂症。此外，当出现严重的行为异常时，作为NMDA受体信号复合物的组分的支架蛋白PSD 95在成年后代的海马体中增加。提示PSD 95可能与精神分裂症的行为异常有关。
Prenatal exposure to polyriboinosinic polyribocytidylic acid (poly I:C) results in psychotic-like behavior in mature rat offspring as well as enduring modifications of glutamatergic excitatory synaptic transmission. However, little is known about the dynamic behavioral and glutamate N-methyl-D-aspartate (NMDA) receptor changes in rat offspring following poly I:C treatment of pregnant dams. In this study, poly I:C was administered to rats intravenously at a dose of 10 mg/kg on gestational day 9 in order to assess changes in behavior and NMDA receptors in offspring over time. Results demonstrate progressive worsening behaviors in adolescents and adults that manifest as increased anxiety, cognitive impairment, and pre-pulse inhibition deficits. Age-related alteration of NMDA receptors in the prefrontal cortex and hippocampus, either total number or distribution, were observed from weaning to adulthood. These results suggest that abnormalities of NMDA receptors occur prior to obvious schizophrenia-like behavioral manifestations. Hence, NMDA receptors may be potential therapeutic targets to prevent disease development during asymptomatic periods of schizophrenia, and may serve as targets for preventive and/or therapeutic strategies for schizophrenia. Further, PSD95, a scaffolding protein that is a component of the NMDA receptor signaling complex, is increased in the hippocampus of adult offspring, when serious behavioral abnormalities emerge. This result suggests that PSD95 may be involved in behavioral abnormalities of schizophrenia.