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骨髓间充质干细胞移植对抽动秽语综合征大鼠刻板行为和多巴胺水平的影响。

Influence of mesenchymal stem cell transplantation on stereotypic behavior and dopamine levels in rats with Tourette syndrome.

机构信息

Department of Pediatrics, Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China.

出版信息

PLoS One. 2013 Apr 26;8(4):e62198. doi: 10.1371/journal.pone.0062198. Print 2013.

DOI:10.1371/journal.pone.0062198
PMID:23638003
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3637366/
Abstract

CONTEXT

Tourette syndrome (TS) is a heterogeneous neuropsychiatric disorder. Chronic motor and phonic tics are central symptoms in TS patients. For some patients, tics are intractable to any traditional treatment and cause lifelong impairment and life-threatening symptoms. New therapies should be developed to address symptoms and overt manifestations of TS. Transplantation of neurogenic stem cells might be a viable approach in TS treatment.

OBJECTIVE

We used mesenchymal stem cell (MSC) transplantation to treat TS. We discuss the mechanism of action, as well as the efficiency of this approach, in treating TS.

SETTINGS AND DESIGN

An autoimmune TS animal model was adopted in the present study. Forty-eight Wistar rats were randomly allocated to the control group and the 2 experimental groups, namely, TS rats+vehicle and TS rats+MSC. MSCs were co-cultured with 5-bromodeoxyuridine (BrdU) for 24 h for labeling prior to grafting.

METHODS

Stereotypic behaviors were recorded at 1, 7, 14, and 28 days after transplantation. Dopamine (DA) content in the striatum of rats in the 3 groups was measured using a high-performance liquid chromatography column equipped with an electrochemical detector (HPLC-ECD) on day 28 after transplantation.

STATISTICAL ANALYSIS

Statistical analysis was performed by repeated measurements analysis of variance to evaluate stereotypic behavior counts at different time points.

RESULTS

TS rats exhibited higher stereotypic behavioral counts compared with the control group. One week after transplantation, TS rats with MSC grafts exhibited significantly decreased stereotypic behavior. Rats with MSC grafts also showed reduced levels of DA in the striatum when compared with TS rats, which were exposed only to the vehicle.

CONCLUSIONS

Intrastriatal transplantation of MSCs can provide relief from the stereotypic behavior of TS. Our results indicate that this approach may have potential for developing therapies against TS. The mechanism(s) of the observed effect may be related to the suppression of DA system by decreasing the content of DA in TS rats.

摘要

背景

妥瑞氏综合征(TS)是一种异质性神经精神障碍。慢性运动性和发音性抽搐是 TS 患者的主要症状。对于一些患者来说,抽搐对任何传统治疗都没有反应,导致终生受损和危及生命的症状。应该开发新的治疗方法来解决 TS 的症状和明显表现。神经源性干细胞移植可能是治疗 TS 的一种可行方法。

目的

我们使用间充质干细胞(MSC)移植来治疗 TS。我们讨论了这种方法的作用机制以及在治疗 TS 中的效率。

设置和设计

本研究采用自身免疫性 TS 动物模型。48 只 Wistar 大鼠随机分为对照组和 2 个实验组,即 TS 大鼠+载体和 TS 大鼠+MSC。将 MSC 与 5-溴脱氧尿苷(BrdU)共培养 24 小时进行标记,然后进行移植。

方法

在移植后 1、7、14 和 28 天记录刻板行为。在移植后第 28 天,使用配备电化学检测器的高效液相色谱柱(HPLC-ECD)测量 3 组大鼠纹状体中的多巴胺(DA)含量。

统计分析

采用重复测量方差分析对不同时间点的刻板行为计数进行统计学分析。

结果

TS 大鼠的刻板行为计数明显高于对照组。移植后 1 周,MSC 移植的 TS 大鼠刻板行为明显减少。与仅接受载体的 TS 大鼠相比,MSC 移植的大鼠纹状体中的 DA 水平也降低。

结论

纹状体内移植 MSC 可以缓解 TS 的刻板行为。我们的结果表明,这种方法可能有潜力开发针对 TS 的治疗方法。观察到的效果的机制可能与通过降低 TS 大鼠中 DA 的含量来抑制 DA 系统有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763f/3637366/065c69a11cc6/pone.0062198.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763f/3637366/70636567517b/pone.0062198.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763f/3637366/7eac728eb348/pone.0062198.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763f/3637366/52bca806e8ab/pone.0062198.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763f/3637366/065c69a11cc6/pone.0062198.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763f/3637366/70636567517b/pone.0062198.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763f/3637366/7eac728eb348/pone.0062198.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763f/3637366/52bca806e8ab/pone.0062198.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/763f/3637366/065c69a11cc6/pone.0062198.g004.jpg

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