Characterization of the cognitive impairments induced by prenatal exposure to stress in the rat
Characterization of the cognitive impairments induced by prenatal exposure to stress in the rat
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DOI：
10.3389/fnbeh.2010.00173
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发表时间：
2010-01-01
影响因子：
3
通讯作者：
Koenig, James I.
中科院分区：
文献类型：
--
作者：
Markham, Julie A.;Taylor, Adam R.;Koenig, James I.
我们先前已经表明，雄性大鼠暴露于妊娠应激表现出类似于精神分裂症中观察到的表型，包括对安非他明的超敏反应，感觉门控迟钝，社会行为中断，应激轴调节受损，以及参与突触可塑性的基因的异常前额叶表达。怀孕期间的母亲心理压力与儿童的不良认知结果有关，并增加了患精神分裂症的风险，其特征是显著的认知缺陷。我们试图使用临床前范式来描述产前应激的长期认知结果，这种范式很容易适应新的治疗策略的发展。在妊娠第三周期间暴露于重复可变产前应激的大鼠使用一系列认知测试进行评估，包括新物体识别任务、线索和背景恐惧条件反射、Morris水迷宫和迭代版本的范例，其中可以评估物体和空间位置的工作记忆和参考记忆（“Can Test”）。产前强调男性受损相对于这些任务的控制，确认这一临床前范式的表面有效性和扩展的认知影响产前应激暴露超出海马。有趣的是，在包括两性的实验中，女性的表现被发现比男性受产前压力的影响更小。这可能与发现女性比男性更不易患精神分裂症有关，值得进一步调查。
We have previously shown that male rats exposed to gestational stress exhibit phenotypes resembling what is observed in schizophrenia, including hypersensitivity to amphetamine, blunted sensory gating, disrupted social behavior, impaired stress axis regulation, and aberrant prefrontal expression of genes involved in synaptic plasticity. Maternal psychological stress during pregnancy has been associated with adverse cognitive outcomes among children, as well as an increased risk for developing schizophrenia, which is characterized by significant cognitive deficits. We sought to characterize the long-term cognitive outcome of prenatal stress using a preclinical paradigm, which is readily amenable to the development of novel therapeutic strategies. Rats exposed to repeated variable prenatal stress during the third week of gestation were evaluated using a battery of cognitive tests, including the novel object recognition task, cued and contextual fear conditioning, the Morris water maze, and iterative versions of a paradigm in which working and reference memory for both objects and spatial locations can be assessed (the "Can Test"). Prenatally stressed males were impaired relative to controls on each of these tasks, confirming the face validity of this preclinical paradigm and extending the cognitive implications of prenatal stress exposure beyond the hippocampus. Interestingly, in experiments where both sexes were included, the performance of females was found to be less affected by prenatal stress compared to that of males. This could be related to the finding that women are less vulnerable than men to schizophrenia, and merits further investigation.