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帕金森病治疗的一个潜在靶点:外侧缰核损伤的影响

A potential target for the treatment of Parkinson's disease: effect of lateral habenula lesions.

作者信息

Han Bing, Jin Hui Juan, Song Mei Ying, Wang Tian, Zhao Hua

机构信息

Neuroscience Research Center, First Hospital of Jilin University, Changchun 130021, China; Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.

Department of Physiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, China.

出版信息

Parkinsonism Relat Disord. 2014 Nov;20(11):1191-5. doi: 10.1016/j.parkreldis.2014.08.022. Epub 2014 Sep 1.

Abstract

OBJECTIVE

Parkinson's disease (PD) is a progressive neurodegenerative movement disorder that is caused predominantly by the degeneration of the nigrostriatal dopaminergic pathway. Lateral habenula (LHb) has efferent projections that terminate in the substantia nigra pars compacta (SNpc) and electrical stimulation of the LHb effectively suppresses the activity of dopamine-containing neurons in the SNpc. This study was aimed to investigate whether LHb lesions can ameliorate the syndromes of PD via affecting the activities of SNpc neurons in 6-hydroxydopamine (6-OHDA)-induced PD model rats.

METHODS

Concentrations of dopamine (DA) and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum, which is the area projected by the SNpc dopaminergic neurons were assayed by high-performance liquid chromatography (HPLC) coupled with fluorescence detection. The immunohistochemical method was applied to detect the numbers of tyrosine hydroxylase (TH)-positive cells in the substantia nigra.

RESULTS

The results showed that LHb lesions induced a significant reduction in apomorphine-induced rotational behavior. The DA, DOPAC and HVA levels in the striatum of PD model rats were increased by the LHb lesions.

CONCLUSION

Therefore, we speculate that the LHb lesions induced a significant amelioration in motor disorders via increasing the DA levels in the striatum, which may lead to a potential therapeutic strategy for the treatment of PD.

摘要

目的

帕金森病(PD)是一种进行性神经退行性运动障碍,主要由黑质纹状体多巴胺能通路的退化引起。外侧缰核(LHb)有传出投射终止于黑质致密部(SNpc),电刺激LHb可有效抑制SNpc中含多巴胺神经元的活动。本研究旨在探讨LHb损伤是否能通过影响6-羟基多巴胺(6-OHDA)诱导的PD模型大鼠中SNpc神经元的活动来改善PD综合征。

方法

采用高效液相色谱(HPLC)结合荧光检测法测定纹状体中多巴胺(DA)及其代谢产物二羟基苯乙酸(DOPAC)和高香草酸(HVA)的浓度,纹状体是SNpc多巴胺能神经元投射的区域。应用免疫组织化学方法检测黑质中酪氨酸羟化酶(TH)阳性细胞的数量。

结果

结果显示,LHb损伤导致阿扑吗啡诱导的旋转行为显著减少。LHb损伤使PD模型大鼠纹状体中的DA、DOPAC和HVA水平升高。

结论

因此,我们推测LHb损伤通过增加纹状体中的DA水平显著改善了运动障碍,这可能为PD的治疗带来一种潜在的治疗策略。

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