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2ISTerre - Institut des Sciences de la Terre (ISTerre, OSUG-C (Maison des Géosciences), 1381, rue de la Piscine, 38610 GIERES
ISTerre, Université Savoie Mont Blanc, Campus Scientifique, 73376 Le Bourget-du-Lac Cedex - France)
Abstract : 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 endo-plasmic reticula. Cytoplasm analysis displays sub-micron Fe/S-rich granules, including lipo-fuscin. 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.
https://hal-cnrs.archives-ouvertes.fr/hal-02879375 Contributor : Laurence LemelleConnect in order to contact the contributor Submitted on : Friday, September 25, 2020 - 3:55:47 PM Last modification on : Thursday, June 9, 2022 - 8:20:08 AM Long-term archiving on: : Thursday, December 3, 2020 - 6:07:01 PM
Laurence Lemelle, Alexandre S. Simionovici, Philippe Colin, Graham Knott, Sylvain Bohic, et al.. Nano-imaging trace elements at organelle levels in substantia nigra overexpressing α-synuclein to model Parkinson’s disease.. Communications Biology, Nature Publishing Group, 2020, 3 (1), ⟨10.1038/s42003-020-1084-0⟩. ⟨hal-02879375⟩