Neuropeptides are important signalling molecules in the brain and alterations in their expression levels have been linked to neurological disorders such as Parkinson's disease. It is challenging to map neuropeptide changes across and within brain regions because of their low in vivo concentrations and complex post-translational processing. Consequently, the role of neuropeptides in Parkinson's disease is not well understood. Thus, we have developed and evaluated a method to image multiple neuropeptides simultaneously in both rat and primate brain tissue sections by matrix-assisted laser desorption/ionisation mass spectrometry imaging at high lateral resolution. Using a unilateral 6-hydroxydopamine rat model of Parkinson's disease, we imaged changes in enkephalins, dynorphins, tachykinins and neurotensin associated with the dopaminergic denervation and L-DOPA treatment in multiple brain regions. L-DOPA administration significantly affected neuropeptides in the globus pallidus, while neuropeptides in the caudate-putamen were mostly affected by dopamine depletion. Using high lateral resolution imaging, we observed an increase of neurotensin in the dorsal sub-region of the globus pallidus after dopamine depletion. This study highlights the capacity of mass spectrometry imaging to elucidate the dynamics of neuropeptide signalling during Parkinson's disease and its treatment.

中文翻译：

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大脑中多个神经肽的同步质谱成像以及实验性帕金森病和L-DOPA治疗引起的改变。

神经肽是大脑中重要的信号分子，其表达水平的改变与帕金森氏病等神经系统疾病有关。由于神经肽的体内浓度低和复杂的翻译后加工过程，很难在整个大脑区域内和内部绘制神经肽变化图。因此，人们对神经肽在帕金森氏病中的作用还不甚了解。因此，我们已经开发和评估了一种通过矩阵辅助激光解吸/电离质谱成像以高横向分辨率同时在大鼠和灵长类动物脑组织切片中同时成像多个神经肽的方法。我们使用帕金森氏病的单侧6-羟基多巴胺大鼠模型，对脑啡肽，强啡肽，速激肽和神经降压素与多脑区神经多巴胺能去神经和L-DOPA治疗相关。L-DOPA给药显着影响苍白球中的神经肽，而尾状-丘脑中的神经肽主要受多巴胺消耗的影响。使用高横向分辨率成像，我们观察到多巴胺耗竭后，苍白球背侧亚区的神经降压素增加。这项研究突出了质谱成像的能力，以阐明帕金森氏病及其治疗过程中神经肽信号传导的动态。使用高横向分辨率成像，我们观察到多巴胺耗竭后，苍白球背侧亚区的神经降压素增加。这项研究突出了质谱成像的能力，以阐明帕金森氏病及其治疗过程中神经肽信号传导的动态。使用高横向分辨率成像，我们观察到多巴胺耗竭后，苍白球背侧亚区的神经降压素增加。这项研究突出了质谱成像的能力，以阐明帕金森氏病及其治疗过程中神经肽信号传导的动态。