Sub-cellular trace element quantifications of nano-heterogeneities in brain tissues offer unprecedented ways to explore at elemental level the interplay between cellular compartments in neurodegenerative pathologies. We designed a quasi-correlative method for analytical nanoimaging of the substantia nigra, based on transmission electron microscopy and synchrotron X-ray fluorescence. It combines ultrastructural identifications of cellular compartments and trace element nanoimaging near detection limits, for increased signal-to-noise ratios. Elemental composition of different organelles is compared to cytoplasmic and nuclear compartments in dopaminergic neurons of rat substantia nigra. They exhibit 150–460 ppm of Fe, with P/Zn/Fe-rich nucleoli in a P/S-depleted nuclear matrix and Ca-rich rough endoplasmic reticula. Cytoplasm analysis displays sub-micron Fe/S-rich granules, including lipofuscin. Following AAV-mediated overexpression of α-synuclein protein associated with Parkinson’s disease, these granules shift towards higher Fe concentrations. This effect advocates for metal (Fe) dyshomeostasis in discrete cytoplasmic regions, illustrating the use of this method to explore neuronal dysfunction in brain diseases.

脑组织中纳米异质性的亚细胞微量元素定量分析提供了前所未有的方法，可以在元素水平上探索神经退行性病变中细胞区室之间的相互作用。我们基于透射电子显微镜和同步加速器X射线荧光设计了一种准相关方法，用于分析黑质的纳米成像。它结合了细胞隔室的超微结构识别和接近检测极限的痕量元素纳米成像，可提高信噪比。比较大鼠黑质多巴胺能神经元中不同细胞器的元素组成与细胞质和核区室。它们表现出150-460 ppm的铁，在贫P / S的核基质和富Ca的粗面内质网中具有富含P / Zn / Fe的核仁。细胞质分析显示亚微米的富含Fe / S的颗粒，包括脂褐素。在AAV介导的与帕金森氏病有关的α-突触核蛋白过表达后，这些颗粒向高铁浓度转移。此效应提倡在离散的细胞质区域中发生金属（Fe）动态平衡，说明使用此方法探索脑部疾病的神经元功能障碍。