Nano-imaging Trace Elements at Organelle Levels in Substantia Nigra Overexpressing α-synuclein to Model Parkinson's Disease

Overview

Journal Commun Biol

Specialty Biology

Date 2020 Jul 11

PMID 32647232

Citations 4

Authors

Laurence Lemelle

Alexandre Simionovici

Philippe Colin

Graham Knott

Sylvain Bohic

Peter Cloetens

Bernard L Schneider

Affiliations

Soon will be listed here.

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 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.

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