Jeon Sang-Chan, Kim Hye-Ji, Ko Eun-A, Jung Sung-Cherl
Department of Physiology, School of Medicine, Jeju National University, Jeju 63243, Korea.
Interdisciplinary Graduate Program in Advanced Convergence Technology & Science, Jeju National University, Jeju 63243, Korea.
Exp Neurobiol. 2021 Feb 28;30(1):87-100. doi: 10.5607/en20057.
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.
在重度抑郁症患者中经常观察到血液中皮质醇水平较高，并且皮质醇水平升高会在动物模型中诱发类似抑郁的症状。然而，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仍不清楚。在本研究中，我们通过在孕期皮下重复注射皮质酮（Corti. Mom，20毫克/千克/天）来提高大鼠的皮质醇水平，并在断奶后立即进行的时期（出生后第21至25天），通过强迫游泳（FS）、旷场（OF）、高架十字迷宫（EPM）和莫里斯水迷宫（MWM）测试评估其幼崽（Corti.Pups）的行为模式。结果显示，皮质酮显著提高了Corti.Moms和Corti.Pups的血浆皮质醇水平。与抑郁动物模型不同，Corti.Pups在FS和OF测试中表现出比用盐水处理的大鼠（Nor.Moms）所生的正常幼崽（Nor.Pups）更高的多动行为。此外，Corti.Pups在EPM测试的开放臂中花费更多时间并行走更长距离，表现出更高的兴奋性。这些模式与注意力缺陷多动障碍（ADHD）动物模型中观察到的行为症状一致，ADHD的特征是多动、冲动和注意力不集中。此外，Corti.Pups在MWM测试中游泳时间更长、距离更远以逃避，显示出与注意力缺陷相关的认知下降。我们的研究结果提供了证据，表明孕期母亲的皮质醇水平可能会影响后代的神经内分泌调节和大脑发育，导致诸如ADHD等异质性发育性脑疾病。
