Mueller Bridget R, Bale Tracy L
Department of Animal Biology, University of Pennsylvania, 201E Vet School, 3800 Spruce Street, Philadelphia, PA 19104, United States.
Physiol Behav. 2007 May 16;91(1):55-65. doi: 10.1016/j.physbeh.2007.01.017. Epub 2007 Feb 8.
Diseases involving cognitive disorders and maladaptive stress-coping behaviors including autism and schizophrenia are present in children born to mothers exposed to stress during pregnancy. To determine the gestational time window when stress exposure produces the greatest impact on cognition, dams were exposed to chronic variable stress (CVS) early, mid-, or late in gestation and offspring learning performance and navigation strategies assessed. These studies utilized a modified version of the Barnes maze to allow investigation of coping responses to stress stimuli. In our study, males exposed to early gestational stress showed significantly impaired learning performance, requiring twice as long to locate the target following training. In stark contrast, early prenatal stress enhanced female performance, where these females located the target in a quarter of the time required by controls. Differences in search strategies whether cued, random, or serial accounted for divergent performances between sex and CVS groups. While control males' behavior expectedly evolved to a cued strategy, the early stressed offspring continued to rely on serial and random searching. Surprisingly, in a long-term memory recall test 6 weeks following previous maze exposure, these early stressed offspring now located the target significantly faster than controls suggesting gestational effects of stress on memory retention that were specific to prenatal time window of stress exposure. Overall, these results provide important insight into the temporal specificity of the effects of prenatal CVS revealing a remarkable vulnerability during early development and a sexually dichotomous influence on cognitive abilities and stress-coping strategies.
患有认知障碍和适应不良应激应对行为的疾病，包括自闭症和精神分裂症，在孕期暴露于应激的母亲所生的孩子中存在。为了确定应激暴露对认知产生最大影响的孕期时间窗口，在妊娠早期、中期或晚期将母鼠暴露于慢性可变应激（CVS），并评估后代的学习表现和导航策略。这些研究使用了改良版的巴恩斯迷宫，以研究对应激刺激的应对反应。在我们的研究中，暴露于妊娠早期应激的雄性后代表现出明显受损的学习表现，训练后找到目标所需的时间是对照组的两倍。与之形成鲜明对比的是，产前早期应激提高了雌性后代的表现，这些雌性找到目标的时间仅为对照组所需时间的四分之一。无论是线索式、随机式还是序列式的搜索策略差异，都导致了性别和CVS组之间的不同表现。虽然对照组雄性的行为预期会演变为线索式策略，但早期应激的后代继续依赖序列式和随机式搜索。令人惊讶的是，在先前迷宫暴露6周后的长期记忆回忆测试中，这些早期应激的后代现在找到目标的速度明显快于对照组，这表明应激对记忆保持的孕期影响特定于应激暴露的产前时间窗口。总体而言，这些结果为产前CVS影响的时间特异性提供了重要见解，揭示了早期发育过程中显著的脆弱性以及对认知能力和应激应对策略的性别二分法影响。
