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Prenatal Exposure to High Cortisol Induces ADHD-like Behaviors with Delay in Spatial Cognitive Functions during the Post-weaning Period in Rats.
Experimental Neurobiology ( IF 2.4 ) Pub Date : 2021-2-27 , DOI: 10.5607/en20057
Sang-Chan Jeon 1 , Hye-Ji Kim 1 , Eun-A Ko 1 , Sung-Cherl Jung 1, 2, 3
Affiliation  

High levels of cortisol in blood are frequently observed in patients with major depressive disorders and increased cortisol level induces depressivelike symptoms in animal models. However, it is still unclear whether maternal cortisol level during pregnancy is a critical factor resulting in neuropsychiatric disorders in offspring. In this study, we increased cortisol level in rats by repetitively injecting corticosterone subcutaneously (Corti. Mom, 20 mg/kg/day) during pregnancy and evaluated the behavioral patterns of their pups (Corti.Pups) via forced swimming (FS), open field (OF), elevated plus maze (EPM) and Morris water maze (MWM) tests during the immediate post-weaning period (postnatal day 21 to 25). In results, corticosterone significantly increased plasma cortisol levels in both Corti.Moms and Corti.Pups. Unlike depressive animal models, Corti.Pups showed higher hyperactive behaviors in the FS and OF tests than normal pups (Nor.Pups) born from rats (Nor.Moms) treated with saline. Furthermore, Corti.Pups spent more time and traveled longer distance in the open arms of EPM test, exhibiting higher extremity. These patterns were consistent with behavioral symptoms observed in animal models of attention deficit hyperactivity disorder (ADHD), which is characterized by hyperactivity, impulsivity, and inattention. Additionally, Corti.Pups swam longer and farther to escape in MWM test, showing cognitive declines associated with attention deficit. Our findings provide evidence that maternal cortisol level during pregnancy may affect the neuroendocrine regulation and the brain development of offspring, resulting in heterogeneous developmental brain disorders such as ADHD.

中文翻译:

产前暴露于高皮质醇会在断奶后大鼠诱发ADHD样行为,并延缓空间认知功能。

在患有严重抑郁症的患者中经常观察到血液中皮质醇水平高,而皮质醇水平升高会在动物模型中引起抑郁样症状。然而,仍不清楚孕期母亲的皮质醇水平是否是导致后代神经精神疾病的关键因素。在这项研究中,我们通过在怀孕期间反复皮下注射皮质酮(Corti。Mom,20 mg / kg /天)来提高大鼠的皮质醇水平,并通过强迫游泳(FS)评估它们的幼崽(Corti.Pups)的行为模式断奶后立即(出生后第21至25天)进行田间(OF),高架迷宫(EPM)和莫里斯水迷宫(MWM)测试。结果,皮质酮显着增加了Corti.Moms和Corti.Pups的血浆皮质醇水平。与抑郁的动物模型不同,在FS和OF测试中,Corti.Pups表现出比由生理盐水处理的大鼠(Nor.Moms)出生的正常幼犬(Nor.Pups)更高的多动行为。此外,Corti.Pups在EPM测试的张开双臂中花费了更多的时间并走了更长的距离,表现出更高的肢体。这些模式与在注意缺陷多动障碍(ADHD)动物模型中观察到的行为症状相一致,该模型的特征在于多动,冲动和注意力不集中。此外,Corti.Pups幼崽游动的时间越来越长,在MWM测试中逃脱,显示出与注意力不足相关的认知能力下降。我们的发现提供了证据,证明孕期母亲的皮质醇水平可能会影响神经内分泌调节和后代的大脑发育,从而导致异质性发育性脑部疾病,例如ADHD。在FS和OF测试中,幼犬表现出比用生理盐水处理的大鼠(Nor.Moms)出生的正常幼犬(Nor.Pups)更高的过度活跃行为。此外,Corti.Pups在EPM测试的张开双臂中花费了更多的时间并走了更长的距离,表现出更高的肢体。这些模式与在注意缺陷多动障碍(ADHD)动物模型中观察到的行为症状相一致,该模型的特征在于多动,冲动和注意力不集中。此外,Corti.Pups幼崽游动的时间越来越长,在MWM测试中逃脱,显示出与注意力不足相关的认知能力下降。我们的发现提供了证据,证明孕期母亲的皮质醇水平可能会影响神经内分泌调节和后代的大脑发育,从而导致异质性发育性脑部疾病,例如ADHD。在FS和OF测试中,幼犬表现出比用生理盐水处理的大鼠(Nor.Moms)出生的正常幼犬(Nor.Pups)更高的过度活跃行为。此外,Corti.Pups在EPM测试的张开双臂中花费了更多的时间并走了更长的距离,表现出更高的肢体。这些模式与在注意缺陷多动障碍(ADHD)动物模型中观察到的行为症状相一致,该模型的特征在于多动,冲动和注意力不集中。此外,Corti.Pups幼崽游动的时间越来越长,在MWM测试中逃脱,显示出与注意力不足相关的认知能力下降。我们的发现提供了证据,证明孕期母亲的皮质醇水平可能会影响神经内分泌调节和后代的大脑发育,从而导致异质性发育性脑部疾病,例如ADHD。
更新日期:2021-03-01
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