Methamphetamine (METH) produces a cytopathology, which is rather specific within catecholamine neurons both in vitro and ex vivo, in animal models and chronic METH abusers. This led some authors to postulate a sort of parallelism between METH cytopathology and cell damage in Parkinson’s disease (PD). In fact, METH increases and aggregates alpha-syn proto-fibrils along with producing spreading of alpha-syn. Although alpha-syn is considered to be the major component of aggregates and inclusions developing within diseased catecholamine neurons including classic Lewy body (LB), at present, no study provided a quantitative assessment of this protein in situ, neither following METH nor in LB occurring in PD. Similarly, no study addressed the quantitative comparison between occurrence of alpha-syn and other key proteins and no investigation measured the protein compared with non-protein structure within catecholamine cytopathology. Therefore, the present study addresses these issues using an oversimplified model consisting of a catecholamine cell line where the novel approach of combined light and electron microscopy (CLEM) was used measuring the amount of alpha-syn, which is lower compared with p62 or poly-ubiquitin within pathological cell domains. The scenario provided by electron microscopy reveals unexpected findings, which are similar to those recently described in the pathology of PD featuring packing of autophagosome-like vesicles and key proteins shuttling autophagy substrates. Remarkably, small seed-like areas, densely packed with p62 molecules attached to poly-ubiquitin within wide vesicular domains occurred. The present data shed new light about quantitative morphometry of catecholamine cell damage in PD and within the addicted brain.

甲基苯丙胺 (METH) 会产生一种细胞病理学，这种细胞病理学在动物模型和慢性甲基苯丙胺滥用者的体外和离体儿茶酚胺神经元中都具有相当的特异性。这导致一些作者假设冰毒细胞病理学与帕金森病 (PD) 中的细胞损伤之间存在某种平行关系。事实上，METH 会增加并聚集 α-syn 原纤维，同时产生 α-syn 的扩散。尽管 α-syn 被认为是包括经典路易体 (LB) 在​​内的患病儿茶酚胺神经元内形成的聚集体和内含物的主要成分，但目前还没有研究对这种蛋白质进行原位定量评估，无论是在 METH 发生后还是在 LB 发生时在PD。同样，没有研究涉及 α-syn 和其他关键蛋白质的出现之间的定量比较，也没有研究在儿茶酚胺细胞病理学中测量该蛋白质与非蛋白质结构的比较。因此，本研究使用由儿茶酚胺细胞系组成的过于简化的模型来解决这些问题，其中使用组合光学和电子显微镜（CLEM）的新方法来测量α-syn的量，与p62或多聚体相比，α-syn的量较低。病理细胞域内的泛素。电子显微镜提供的场景揭示了意想不到的发现，这与最近在 PD 病理学中描述的类似，其特征是自噬体样囊泡和穿梭自噬底物的关键蛋白质的堆积。值得注意的是，出现了小的种子状区域，在宽的囊泡域内密集地填充有附着在多聚泛素上的 p62 分子。目前的数据为PD和成瘾大脑内儿茶酚胺细胞损伤的定量形态测量提供了新的线索。