Abstract

Aim

Besides motor impairment, non-motor symptoms including cognitive decline, anxiety, and depression are observed in Parkinson’s Disease (PD). The aim of this study was to investigate whether chronic administration of central neuropeptide-S (NPS) improves non-motor symptoms in 6-hydroxydopamine (6-OHDA)-induced parkinsonian rats.

Material and methods

Experimental PD was utilized by unilateral stereotaxic injection of the 6-OHDA into the medial forebrain bundle (MFB), while the sham-operated animals underwent the same surgical procedures. NPS (1 nmol) or vehicle was daily administered through an intracerebroventricular (icv) cannula for 7 days. Radial arm maze (RAM) test was used to evaluate the working memory; whereas, elevated plus maze (EPM) test and sucrose preference test were used to monitor the anxiety and depression status, respectively. The levels of dopamine, glutamic acid, and glutamine was determined in harvested striatal and hippocampal tissue samples. The immunoreactivities for tyrosine hydroxylase (TH) was determined using immunohistochemistry.

Results

In the RAM test, the 6-OHDA-induced increases in the reference and working memory errors were reduced by the central NPS administration. The decreased sucrose preference in the parkinsonian rats was increased by centrally administered NPS. The levels of dopamine levels in striatum and hippocampus were decreased in the parkinsonian rats, however, they were not altered by the centrally administered NPS. Additionally, NPS treatment significantly attenuated the 6-OHDA-induced loss of TH neuronal number.

Conclusion

Consequently, NPS appears to be a therapeutic candidate for the treatment of non-motor complications of PD.

中文翻译：

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慢性神经肽-S治疗对帕金森病实验模型非运动参数的影响

 抽象的

 目的

除了运动障碍外，帕金森病 (PD) 还观察到非运动症状，包括认知能力下降、焦虑和抑郁。本研究的目的是调查长期给予中枢神经肽-S (NPS) 是否可以改善 6-羟基多巴胺 (6-OHDA) 诱导的帕金森病大鼠的非运动症状。

 材料与方法

通过将 6-OHDA 单侧立体定位注射到内侧前脑束 (MFB) 来进行实验性 PD，而假手术动物则接受相同的手术程序。每天通过脑室内 (icv) 插管施用 NPS (1 nmol) 或载体，持续 7 天。采用径向臂迷宫（RAM）测试评估工作记忆；而高架十字迷宫（EPM）测试和蔗糖偏好测试分别用于监测焦虑和抑郁状态。在收集的纹状体和海马组织样本中测定多巴胺、谷氨酸和谷氨酰胺的水平。使用免疫组织化学测定酪氨酸羟化酶（TH）的免疫反应性。

 结果

在 RAM 测试中，中央 NPS 管理减少了 6-OHDA 引起的参考和工作记忆错误的增加。中央给予 NPS 可以增加帕金森病大鼠对蔗糖偏好的降低。帕金森病大鼠纹状体和海马的多巴胺水平降低，但中央施用的 NPS 并未改变它们。此外，NPS 治疗显着减轻了 6-OHDA 诱导的 TH 神经元数量损失。

 结论

因此，NPS 似乎是治疗 PD 非运动并发症的候选治疗药物。