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5-羟色胺耗竭对大鼠行为和神经元氧化应激状态的影响:与焦虑和情感障碍的相关性。

Effects of serotonin depletion on behavior and neuronal oxidative stress status in rat: relevance for anxiety and affective disorders.

机构信息

"Alexandru Ioan Cuza" University, Iasi, Romania.

出版信息

Adv Med Sci. 2010;55(2):289-96. doi: 10.2478/v10039-010-0035-2.

DOI:10.2478/v10039-010-0035-2
PMID:20934963
Abstract

PURPOSE

We lesioned the hypothalamic paraventricular nucleus (PVN) of male Wistar rats using two different doses (8μg/3μl and 16μg/3μl) of 5,7-dihydroxytryptamine (5,7-DHT) and then animals were subjected to a battery of behavioral tests designed to assess anxiety and memory formation. Further, we were interested to know whether this lesion would result in neuronal oxidative stress and also if there is a correlation between the behavioral response to this lesion and brain oxidative stress.

MATERIAL/METHODS: Behavioral tests included elevated plus maze, used to assess exploration/anxiety status and radial armmaze, used for determining spatial short-term and reference memory errors. Regarding the oxidative stress, we measured the extent of some lipid peroxidation products like malondialdehyde and defense enzymes such as superoxide dismutase and glutathione peroxidase.

RESULTS

5,7-DHT lesioned rats spent more time in the open arms of the elevated maze compared to sham-operated rats, suggesting that the lesion significantly diminished anxiety-like behavior. Also, short-term memory was significantly impaired, as shown by the working memory errors in radial arm-maze task. Further analyses revealed that the 5,7-DHT lesion did not result in a significant change of reference memory errors. Regarding the oxidative stress, no significant modification of both superoxide dismutase and glutathione peroxidase specific activities from the temporal lobe were observed. However, the malondiadehyde level was significantly increased, suggesting pro-oxidant effects. Also, the linear regression between the working memory errors vs. malondiadehyde resulted in significant correlations.

CONCLUSION

5,7 DHT lesion of the PVN affects behavioral performance via interactions with systems governing novel and/or fear-evoking situations and also by increasing neuronal oxidative stress.

摘要

目的

我们使用两种不同剂量(8μg/3μl 和 16μg/3μl)的 5,7-二羟基色胺(5,7-DHT)损伤雄性 Wistar 大鼠的下丘脑室旁核(PVN),然后对动物进行一系列行为测试,旨在评估焦虑和记忆形成。此外,我们还想知道这种损伤是否会导致神经元氧化应激,以及这种损伤对行为反应与大脑氧化应激之间是否存在相关性。

材料/方法:行为测试包括高架十字迷宫,用于评估探索/焦虑状态和放射臂迷宫,用于确定空间短期和参考记忆错误。关于氧化应激,我们测量了一些脂质过氧化产物的程度,如丙二醛以及防御酶,如超氧化物歧化酶和谷胱甘肽过氧化物酶。

结果

与假手术大鼠相比,5,7-DHT 损伤大鼠在高架迷宫的开放臂中花费的时间更多,这表明损伤显著减轻了焦虑样行为。此外,短期记忆也明显受损,表现为放射臂迷宫任务中的工作记忆错误。进一步的分析表明,5,7-DHT 损伤并未导致颞叶中超氧化物歧化酶和谷胱甘肽过氧化物酶特定活性的显著变化。然而,丙二醛水平显著增加,表明存在促氧化剂作用。此外,工作记忆错误与丙二醛之间的线性回归呈显著相关性。

结论

PVN 的 5,7-DHT 损伤通过与控制新情景和/或恐惧情景的系统相互作用,以及通过增加神经元氧化应激,影响行为表现。

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