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糖皮质激素/糖皮质激素受体对多动症大鼠多巴胺能神经递质的影响。

Glucocorticoids/glucocorticoid receptors effect on dopaminergic neurotransmitters in ADHD rats.

作者信息

Chen Yanhui, Zheng Xiaolan, Xie Linqi, Huang Liang, Ke Zhongling, Zheng Jie, Lu Hongzhu, Hu Jun

机构信息

Department of Pediatrics, Fujian Medical University Union Hospital, Fuzhou, 350001, China.

Department of Pediatrics, Fujian Medical University Union Hospital, Fuzhou, 350001, China.

出版信息

Brain Res Bull. 2017 May;131:214-220. doi: 10.1016/j.brainresbull.2017.04.013. Epub 2017 Apr 27.

Abstract

Dexamethaone (DEX, glucocorticoid receptor agonist) and RU486 (glucocorticoid receptor inhibitor) may affect the behavior of attention deficit hyperactivity disorder (ADHD) rats, by changing the level of dopamine and noradrenaline and dopamine transporter in different regions of their brain. In this study, we have investigated the effect and the underlying mechanism of Glucocorticoids/Glucocorticoid receptors on dopaminergic neurotransmitters in ADHD Rats. Thirty male Wistar Kyoto rats (WKY) and 30 male spontaneously hypertensive rats (SHR) were respectively divided into 3 groups randomly as follows: a GR agonist group (DEX), a GR inhibitor group (RU486) and a control group (CON). Open field test and Y maze were performed respectively to assess the behavior of the rats. The levels of dopamine, norepinephrine, and dopamine transporter (DAT) in the prefrontal cortex and striatum were also tested. Our results showed that, the behavior of rats were improved after DEX treatment. We also found that the level of DA and NE increased in DEX group, but decreased significantly in RU486 group. Immunohistochemical assay showed that DAT expression level in DEX group was significantly less than that in RU486 and CON group. In conclusion, by regulation of glucocorticoid receptor, GR agonist can decrease DAT expression, resulting in the increase of DA and NE levels in brain that ameliorate hyperactivity and attention deficit in ADHD rats. Our results suggest that the effects of glucocorticoid receptor on dopaminergic neurotransmitter in the central nervous system may be involved in the pathogenesis of ADHD.

摘要

地塞米松(DEX,糖皮质激素受体激动剂)和RU486(糖皮质激素受体抑制剂)可能通过改变注意力缺陷多动障碍(ADHD)大鼠大脑不同区域的多巴胺、去甲肾上腺素水平及多巴胺转运体,从而影响其行为。在本研究中,我们探究了糖皮质激素/糖皮质激素受体对ADHD大鼠多巴胺能神经递质的作用及潜在机制。将30只雄性Wistar Kyoto大鼠(WKY)和30只雄性自发性高血压大鼠(SHR)分别随机分为3组:糖皮质激素受体激动剂组(DEX)、糖皮质激素受体抑制剂组(RU486)和对照组(CON)。分别进行旷场试验和Y迷宫试验以评估大鼠行为。同时检测前额叶皮质和纹状体中多巴胺、去甲肾上腺素及多巴胺转运体(DAT)的水平。结果显示,DEX处理后大鼠行为得到改善。我们还发现,DEX组中多巴胺和去甲肾上腺素水平升高,而RU486组则显著降低。免疫组织化学检测显示,DEX组DAT表达水平显著低于RU486组和CON组。综上所述,通过调节糖皮质激素受体,GR激动剂可降低DAT表达,导致脑内多巴胺和去甲肾上腺素水平升高,从而改善ADHD大鼠的多动和注意力缺陷。我们的结果提示,糖皮质激素受体对中枢神经系统多巴胺能神经递质的作用可能参与了ADHD的发病机制。

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