Using a maternal immune stimulation model of schizophrenia to study behavioral and neurobiological alterations over the developmental course
Using a maternal immune stimulation model of schizophrenia to study behavioral and neurobiological alterations over the developmental course
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DOI：
10.1016/j.schres.2015.05.010
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发表时间：
2015-08-01
影响因子：
4.5
通讯作者：
Winter, Christine
中科院分区：
文献类型：
--
作者：
Hadar, Ravit;Luisa Soto-Montenegro, Ma;Winter, Christine
越来越多的证据揭示了精神分裂症的神经发育本质，其症状通常出现在青春期后期或成年早期。我们比较了症状前的青春期与成年期的完整症状期的行为和神经生物学水平的聚I：C母体免疫刺激（MIS）大鼠模型的精神分裂症。我们发现，在MIS-rats受损的感觉运动门控，反映在中断prepusle抑制（PPI），出现青春期后，与行为缺陷只记录在成年期，但不是在青春期。使用死后HPLC，我们发现，MIS-大鼠表现出明显的多巴胺和5-羟色胺的变化，在内侧前额叶皮层（mPFC），核丘脑（Nacc），尾壳核，苍白球，海马。此外，FDG-PET显示，与对照组相比，这些动物在腹侧海马和PFC中具有较低的葡萄糖摄取，而在杏仁核和Nacc中具有较高的代谢。神经传递和代谢活动的变化在不同的大脑结构之间的第一次出现和进一步发展。在mPFC和Hipp，MIS-大鼠表现出异常的神经化学和代谢活动之前，并与青少年和成年状态的行为缺陷的发展，反映了这些地区的早期损伤。相比之下，Nacc和苍白球的生化改变随着年龄的增长而发展。我们的研究结果表明，MIS诱导的神经化学和代谢变化是神经发育的性质，无论是进行性或nonprogressive和行为缺陷表现为这些异常的增加。(C)2015 Elsevier B. V.版权所有。
A growing body of evidence sheds light on the neurodevelopmental nature of schizophrenia with symptoms typically emerging during late adolescence or young adulthood. We compared the pre-symptomatic adolescence period with the full symptomatic period of adulthood at the behavioral and neurobiological level in the poly I:C maternal immune stimulation (MIS) rat model of schizophrenia. We found that in MIS-rats impaired sensorimotor gating, as reflected in disrupted prepusle inhibition (PPI), emerged post-pubertally, with behavioral deficits being only recorded in adulthood but not during adolescence. Using post mortem HPLC we found that MIS-rats show distinct dopamine and serotonin changes in the medial prefrontal cortex (mPFC), nucleus accumbens (Nacc), caudate putamen, globus pallidus, and hippocampus. Further, FDG-PET has shown that these animals had lower glucose uptake in the ventral hippocampus and PFC and a higher metabolism in the amygdala and Nacc when compared to controls. Changes in neurotransmission and metabolic activity varied across brain structures with respect to first appearance and further development. In the mPFC and Hipp, MIS-rats showed abnormal neurochemical and metabolic activity prior to and with the development of behavioral deficits in both adolescent and adult states, reflecting an early impairment of these regions. In contrast, biochemical alteration in the Nacc and globus pallidus developed as a matter of age. Our findings suggest that MIS-induced neurochemical and metabolic changes are neurodevelopmental in nature and either progressive or nonprogressive and that the behavioral deficits manifest as these abnormalities increase. (C) 2015 Elsevier B.V. All rights reserved.