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新生期电离辐射暴露致海马相关记忆损伤和组织学损害及其氧化应激状态的作用

Hippocampal-related memory deficits and histological damage induced by neonatal ionizing radiation exposure. Role of oxidative status.

机构信息

1a Cátedra de Farmacología, Facultad de Medicina, UBA, CEFYBO-CONICET, Argentina.

出版信息

Brain Res. 2010 Feb 2;1312:67-78. doi: 10.1016/j.brainres.2009.11.053. Epub 2009 Nov 27.

DOI:10.1016/j.brainres.2009.11.053
PMID:19948150
Abstract

Ionizing radiations induce oxidative stress on target tissues, mainly through the generation of reactive oxygen species (ROS). However, there are few data available on the behavioral effects of moderate doses of ionizing radiation. The aim of the present work was to evaluate the performance of adult rats irradiated at birth in different hippocampal-dependent behavioral tasks and to establish a relationship with the oxidative status and histological changes in rat hippocampus (Hip). Male Wistar rats were irradiated with 5 Gy of X rays between 24 and 48 h after birth. Thirty days later, rats were subjected to open field, object recognition and inhibitory avoidance tasks. In addition, oxidative status markers as well as protein kinase C (PKC) activity and histological changes were assessed in control and irradiated Hip. Results show an impairment in recognition and habituation memories in 30-day-old animals exposed to neonatal ionizing radiation, both at short- (ST) and at long-term (LT), whereas an improvement in associative memory was observed at ST. In addition, histological alterations were observed in irradiated Hip. Although an increase in ROS levels and PKC activity were found in irradiated Hip, no changes in the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were observed. Taken together, our results support the hypothesis that an increased PKC activity, induced by neonatal ionizing radiation on rat Hip, could play a role in the generation of an imbalance between ROS levels and antioxidant systems and might underlie radiation-induced hippocampal histological damage as well as the Hip-dependent behavioral changes found in irradiated rats.

摘要

电离辐射会在靶组织中诱导氧化应激,主要是通过产生活性氧物种 (ROS)。然而,关于中等剂量电离辐射的行为效应的数据很少。本工作的目的是评估出生时接受辐照的成年大鼠在不同海马依赖性行为任务中的表现,并与大鼠海马 (Hip) 的氧化状态和组织学变化建立关系。雄性 Wistar 大鼠在出生后 24 至 48 小时之间接受 5 Gy X 射线照射。30 天后,大鼠接受旷场、物体识别和抑制性回避任务。此外,还评估了对照和辐照 Hip 中的氧化状态标志物以及蛋白激酶 C (PKC) 活性和组织学变化。结果显示,在短时间内(ST)和长时间内(LT),暴露于新生电离辐射的 30 日龄动物的识别和习惯记忆受损,而在 ST 时观察到联想记忆的改善。此外,在辐照 Hip 中观察到组织学改变。尽管在辐照 Hip 中发现 ROS 水平和 PKC 活性增加,但抗氧化酶超氧化物歧化酶 (SOD) 和过氧化氢酶 (CAT) 没有变化。总之,我们的结果支持这样一种假设,即新生电离辐射诱导的大鼠 Hip 中 PKC 活性的增加可能在 ROS 水平和抗氧化系统之间的失衡产生中起作用,并可能是辐射诱导的海马组织损伤以及在辐照大鼠中发现的海马依赖性行为变化的基础。

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