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与妥瑞氏综合征病理生理机制相关的多巴胺和血清素转运体的异常表达。

Abnormal expression of dopamine and serotonin transporters associated with the pathophysiologic mechanism of Tourette syndrome.

机构信息

Department of Integrated Chinese and Western Medicine on Pediatrics, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.

出版信息

Neurol India. 2010 Jul-Aug;58(4):523-9. doi: 10.4103/0028-3886.68663.

DOI:10.4103/0028-3886.68663
PMID:20739786
Abstract

BACKGROUND

Tourette syndrome (TS) is a neurobehavioral and neuropsychiatric disorder and its pathophysiology is not well understood. However, recent studies provide evidence implicating metabolic abnormalities of dopamine (DA) and serotonin (5-HT) of the basal ganglia both in TS patients and TS animal models. It is also well known that dopamine and serotonin transporters (DAT and SERT) are monoamine neurotransmitter transporters, which participate in the metabolism of DA and 5-HT, respectively.

OBJECTIVE

To evaluate whether expression of DAT and SERT in the striatum could lead to pathophysiological change in TS rat model.

MATERIALS AND METHODS

Twenty-four Wistar male rats were randomly allocated to: TS model group (n=12) and control group (n=12). The stereotypy counts were recorded during the 2-week period of inducing TS rat models. The levels of DA and 5-HT in striatum homogenate were measured by ELISA. The protein and mRNA expression of DAT and SERT in the striatum were tested respectively by Immunofluorescence, Western blot and quantitative real-time PCR. Results : ANOVA analysis indicated that the stereotypy scores were much higher in the TS model group than in the control group at different time points (P<0.01). By ELISA analysis, the DA concentration in striatum homogenate was higher in the TS model group (130.92 +/- 25.60 ng/mL) than in the control group (101.00 +/- 20.14 ng/mL) (P<0.01), but 5-HT concentration in striatum was found to be lower in the TS model group (59.79 +/- 14.73 ng/mL) compared to the control group (77.01 +/- 14.05 ng/mL) (P<0.05). Analysis of protein and mRNA levels revealed a lower expression of DAT, concomitant with a higher expression of SERT in striatum of the TS model group than in the control group.

CONCLUSIONS

Lower expression in DAT, concomitant with higher expression in SERT could participate in the pathophysiology of TS.

摘要

背景

妥瑞氏综合征(TS)是一种神经行为和神经精神疾病,其病理生理学尚不清楚。然而,最近的研究提供了证据,表明基底神经节中多巴胺(DA)和血清素(5-HT)的代谢异常,既存在于 TS 患者中,也存在于 TS 动物模型中。众所周知,多巴胺和血清素转运体(DAT 和 SERT)是单胺神经递质转运体,分别参与 DA 和 5-HT 的代谢。

目的

评估纹状体中 DAT 和 SERT 的表达是否会导致 TS 大鼠模型的病理生理变化。

材料与方法

将 24 只雄性 Wistar 大鼠随机分为:TS 模型组(n=12)和对照组(n=12)。在诱导 TS 大鼠模型的 2 周期间记录刻板行为计数。通过 ELISA 测量纹状体匀浆中 DA 和 5-HT 的水平。通过免疫荧光、Western blot 和定量实时 PCR 分别检测纹状体中 DAT 和 SERT 的蛋白和 mRNA 表达。结果:方差分析表明,在不同时间点,TS 模型组的刻板行为评分明显高于对照组(P<0.01)。通过 ELISA 分析,TS 模型组纹状体匀浆中 DA 浓度(130.92 +/- 25.60 ng/mL)高于对照组(101.00 +/- 20.14 ng/mL)(P<0.01),但 TS 模型组纹状体中 5-HT 浓度(59.79 +/- 14.73 ng/mL)低于对照组(77.01 +/- 14.05 ng/mL)(P<0.05)。蛋白和 mRNA 水平分析显示,TS 模型组纹状体中 DAT 的表达降低,同时 SERT 的表达升高。

结论

DAT 表达降低,同时 SERT 表达升高可能参与了 TS 的病理生理学过程。

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