Long-Lasting Effects of Maternal Separation on an Animal Model of Post-Traumatic Stress Disorder: Effects on Memory and Hippocampal Oxidative Stress

Long-Lasting Effects of Maternal Separation on an Animal Model of Post-Traumatic Stress Disorder: Effects on Memory and Hippocampal Oxidative Stress
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DOI:
10.1007/s11064-011-0660-6
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发表时间:
2012-04-01
影响因子:
4.4
通讯作者:
Dalmaz, Carla
Dalmaz, Carla
中科院分区:
医学3区
文献类型:
--
作者:
Diehl, Luisa A.;Alvares, Lucas O.;Dalmaz, Carla

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早期生活中的不良事件,如定期的母亲分离,可能会改变大脑发育的正常模式,从而改变成年后对各种精神障碍的脆弱性。有早期逆境史的患者表现出更高的创伤后应激障碍(PTSD)频率。本研究旨在验证暴露于创伤后应激障碍动物模型后,幼鼠与母鼠反复长期分离是否会影响记忆和氧化应激参数。将Wistar大鼠的巢分为完整的,并在出生后第1-10天进行母体分离(32 ℃孵育箱,3小时/天)。当成年后,动物被细分为暴露或不暴露于PTSD模型,该模型包括暴露于不可避免的脚震,然后是情景提醒。休克1个月后,进行记忆任务(Morris水迷宫),1个月后处死动物,检测海马区DNA断裂和抗氧化酶活性。暴露于休克或母体分离加休克的大鼠对空间记忆表现出持久的影响,在水迷宫的相反象限花费更多的时间。这种影响在母亲分离和休克的动物中更高。休克和母亲分离诱导海马DNA断裂得分较高。抗氧化酶活性无差异。总之,周期性的母亲分离可能会增加易感性的压力施加在成年后在水迷宫中的性能的影响。增加海马DNA断裂诱导,母亲分离和暴露于休克。
Adverse early life events, such as periodic maternal separation, may alter the normal pattern of brain development and subsequently the vulnerability to a variety of mental disorders in adulthood. Patients with a history of early adversities show higher frequency of post-traumatic stress disorder (PTSD). This study was undertaken to verify if repeated long-term separation of pups from dams would affect memory and oxidative stress parameters after exposure to an animal model of PTSD. Nests of Wistar rats were divided into intact and subjected to maternal separation (incubator at 32 degrees C, 3 h/day) during post-natal days 1-10. When adults, the animals were subdivided into exposed or not to a PTSD model consisting of exposure to inescapable footshock, followed by situational reminders. One month after exposure to the shock, the animals were exposed to a memory task (Morris water maze) and another month later animals were sacrificed and DNA breaks and antioxidant enzymes activities were measured in the hippocampus. Rats exposed to shock or maternal separation plus shock showed long-lasting effects on spatial memory, spending more time in the opposite quadrant of the water maze. This effect was higher in animals subjected to both maternal separation and shock. Both shock and maternal separation induced a higher score of DNA breaks in the hippocampus. No differences were observed on antioxidant enzymes activities. In conclusion, periodic maternal separation may increase the susceptibility to the effects of a stressor applied in adulthood on performance in the water maze. Increased DNA breaks in hippocampus was induced by both, maternal separation and exposure to shock.