Markham Julie A, Taylor Adam R, Taylor Sara B, Bell Dana B, Koenig James I
Department of Psychiatry, Maryland Psychiatric Research Center, University of Maryland-Baltimore School of Medicine Baltimore, MD, USA.
Front Behav Neurosci. 2010 Nov 25;4:173. doi: 10.3389/fnbeh.2010.00173. eCollection 2010.
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.
我们之前已经表明，暴露于孕期应激的雄性大鼠会表现出类似于精神分裂症的表型，包括对安非他明过敏、感觉门控迟钝、社交行为紊乱、应激轴调节受损以及参与突触可塑性的基因在前额叶的异常表达。孕期母亲的心理应激与儿童不良认知结果以及精神分裂症患病风险增加有关，精神分裂症的特征是存在显著的认知缺陷。我们试图使用一种临床前范式来描述产前应激的长期认知结果，这种范式很容易用于开发新的治疗策略。对在妊娠第三周暴露于反复可变产前应激的大鼠进行了一系列认知测试评估，包括新物体识别任务、线索性和情境性恐惧条件反射、莫里斯水迷宫，以及一种可评估物体和空间位置工作记忆及参考记忆的范式的迭代版本（“罐头测试”）。与对照组相比，产前应激的雄性大鼠在上述每项任务中均表现受损，这证实了该临床前范式的表面效度，并将产前应激暴露的认知影响扩展到了海马体之外。有趣的是，在纳入了两性的实验中，发现雌性大鼠的表现受产前应激的影响小于雄性大鼠。这可能与女性比男性更不易患精神分裂症这一发现有关，值得进一步研究。
