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褪黑素增加可能在帕金森病 6-羟多巴胺模型纹状体中起双重作用。

Increased melatonin may play dual roles in the striata of a 6-hydroxydopamine model of Parkinson's disease.

机构信息

Research Center of Neurobiology, Fujian Medical University, Fuzhou 350004, China.

出版信息

Life Sci. 2013 Mar 12;92(4-5):311-6. doi: 10.1016/j.lfs.2013.01.007. Epub 2013 Jan 16.

Abstract

AIMS

To investigate dynamic changes and roles of melatonin (MLT) in the striata of 6-hydroxydopamine (6-OHDA)-treated rats.

MAIN METHODS

A Parkinson's disease (PD) rat was established by a unilateral injection of 6-OHDA into the right substantia nigra pars compacta (SNc) and the right medial forebrain bundle (MFB) to achieve a complete lesion of the ipsilateral nigrostriatal DA system. Dialysates were collected in the lesioned striatum at different time intervals by in vivo microdialysis. In addition, both contralateral and ipsilateral striatum tissues were collected at two time intervals (10:00 and 22:00 h) at 3 and 6 weeks after lesioning. The levels of DA, 3, 4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the dialysates, as well as MLT in the dialysates and tissues were determined using HPLC.

KEY FINDINGS

The dialysate contents of DA, DOPAC and HVA in the lesioned striatum were significantly decreased (P<0.001) in comparison with those in the controls or in the unlesioned side 3 weeks after lesioning while the extracellular level of MLT in the lesioned striatum in these corresponding time intervals distinctly increased when compared with those in the controls (P<0.05). The tissue MLT contents increased in the bilateral striata in different degrees at 6 weeks post-lesion (P<0.05). Moreover, increased MLT levels correlate well with rotations or DA changes in the lesioned striatum.

SIGNIFICANCE

These data suggest that 6-OHDA lesion manipulates the MLT secretion pattern. Increased striatal MLT level by a unilateral intracerebral injection of 6-OHDA may play dual roles in the progression of PD in rats.

摘要

目的

研究褪黑素(MLT)在 6-羟多巴胺(6-OHDA)处理的大鼠纹状体中的动态变化和作用。

方法

通过向右侧黑质致密部(SNc)和内侧前脑束(MFB)单侧注射 6-OHDA 建立帕金森病(PD)大鼠模型,实现同侧黑质纹状体 DA 系统的完全损伤。通过体内微透析在不同时间间隔采集损伤纹状体的透析液。此外,在损伤后 3 周和 6 周的两个时间间隔(10:00 和 22:00 h)采集双侧和同侧纹状体组织。使用 HPLC 测定透析液中 DA、3,4-二羟基苯乙酸(DOPAC)和高香草酸(HVA)的水平以及透析液和组织中的 MLT。

主要发现

与对照组或未损伤侧相比,损伤后 3 周时损伤纹状体中 DA、DOPAC 和 HVA 的透析液含量明显降低(P<0.001),而在相应时间间隔内损伤纹状体中 MLT 的细胞外水平明显高于对照组(P<0.05)。损伤后 6 周,双侧纹状体的组织 MLT 含量均有不同程度的增加(P<0.05)。此外,增加的 MLT 水平与损伤纹状体中的旋转或 DA 变化密切相关。

意义

这些数据表明,6-OHDA 损伤改变了 MLT 的分泌模式。通过单侧脑内注射 6-OHDA 增加纹状体 MLT 水平可能在大鼠 PD 的进展中发挥双重作用。

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