Department of Pediatrics, University of Cincinnati College of Medicine, and Division of Neurology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
Robyn Amos-Kroohs, Virginia Department of Forensic Science, 700 North Fifth St, Richmond, VA 23219, USA.
Neurotoxicol Teratol. 2024 May-Jun;103:107356. doi: 10.1016/j.ntt.2024.107356. Epub 2024 May 7.
Developmental stress, including low socioeconomic status (SES), can induce dysregulation of the hypothalamic-pituitary-adrenal axis and result in long-term changes in stress reactivity. Children in lower SES conditions often experience more stress than those in other SES groups. There are multiple model systems of early environmental stress (EES), one of which is reduced cage bedding. Here we tested the effects of both prenatal and lactational EES in rats on a range of long-term behavioral and cognitive outcomes. There were persistent reductions in body weight in the EES rats in both sexes. The behavioral results showed no effects on learning and memory using tests of spatial learning or cognitive flexibility in the Morris water maze, egocentric learning in the Cincinnati water maze, or working memory in the radial-arm maze. There were no effects on basic open-field activity, elevated zero-maze, or forced swim test, but EES rats had reduced time in the dark side of the light/dark test. When rats were drug challenged in the open-field with d-amphetamine or MK-801, there were no differential responses to d-amphetamine, but the EES group under responded compared with the drug-induced hyperactivity in the control group in both males and females. The objective was to establish a developmental stress model that induced cognitive deficits and to the extent that this method did not cause such effects it was not the model we sought. However, the data showed several long-term effects of EES, including the reduced response to the irreversible NMDA antagonist MK-801. This effect merits further investigation.
发展压力,包括低社会经济地位(SES),会导致下丘脑-垂体-肾上腺轴失调,并导致应激反应的长期变化。SES 较低的儿童通常比其他 SES 群体经历更多的压力。有多种早期环境应激(EES)的模型系统,其中一种是减少笼内垫料。在这里,我们测试了产前和哺乳期 EES 对大鼠一系列长期行为和认知结果的影响。在雄性和雌性 EES 大鼠中,体重持续减轻。行为学结果表明,在 Morris 水迷宫中的空间学习或认知灵活性测试、辛辛那提水迷宫中的自我中心学习或放射臂迷宫中的工作记忆中,学习和记忆没有影响。在基本的开阔场活动、高架零迷宫或强迫游泳测试中没有影响,但 EES 大鼠在明暗测试中的黑暗侧停留时间减少。当大鼠在开放场中用 d-苯丙胺或 MK-801 进行药物挑战时,d-苯丙胺没有引起不同的反应,但与对照组相比,EES 组在雄性和雌性大鼠中对药物诱导的过度活动的反应都较低。目的是建立一种诱导认知缺陷的发育性应激模型,在这种方法没有引起这种影响的程度上,它不是我们所寻求的模型。然而,这些数据显示了 EES 的几个长期影响,包括对不可逆 NMDA 拮抗剂 MK-801 的反应降低。这一效应值得进一步研究。