New nanoimaging method traces metal presence in Parkinson’s brain

15-07-2020

Many neurodegenerative diseases like Parkinson’s and Alzheimer's often exhibit an excess of iron in the brain. Scientists have developed a method to trace the presence of metals in brain at the sub-cellular level, particularly in organelles of neurons vulnerable to these diseases. The results are published in Communications Biology.

  • Share

The level and distribution of iron in the brain normally contributes to essential cellular functions, including mitochondrial respiration, via its capability to transfer electrons. In vulnerable populations of neurons however, iron dysregulation can have detrimental effects. Genetic defects affecting iron metabolism cause brain diseases, including Parkinson’s and Alzheimer’s, both associated with iron overload. “It is important to be able to explore metal distribution in neurons and glia (non-neuronal cells), with the aim to identify potential causal mechanisms in neurodegeneration”, explains Bernard Schneider, scientist at EPFL and co-author of the study.

Until now, there was no method that could trace the elements with sensitivity and nanometre resolution. A team of scientists from LGL-TPE (Laboratoire de Géologie de Lyon : Terre, Planètes et Environnement), Institut des Sciences de la terre (ISTerre) de Grenoble, the ESRF and the EPFL (École Polytechnique Fédérale de Lausanne) have now combined the techniques of transmission electron microscopy and synchrotron X-ray fluorescence at the ESRF in order to evaluate the element unbalance in Parkinson’s disease.

They have identified compartments and organelles in a rat cerebral tissue and quantified their elementary composition and, in this way, validated the utility of this method to explore finely dysfunctions of neuronal organelles in cerebral pathologies. “This represents a step forward in understanding the link between metals in brain and neurodegenerative diseases, which is one of the subjects that we are specialized in on our beamline”, explains Peter Cloetens, scientist in charge of ID16A, the beamline used at the ESRF, and co-author of the paper.

Beyond clinical applications

“Besides clinical applications, this new imaging methodology linked to emerging extremely brilliant synchrotron sources opens the way to better understanding of sub-micrometer biogenic (microorganisms, viruses, molecular assemblies) or geological features linked to the origins of life”, says Laurence Lemelle, CNRS scientist at LGL-TPE Lyon, first author of the study. “We developed this method also to analyse meteorites and samples related to the origin of life on Earth and beyond, such as the oldest fossils on Earth. We will also study future Mars sample returns, under quarantine conditions, to look for life”, says Alexandre Simionovici, corresponding author of the study and professor at the Université Grenoble Alpes. And he is excited about the future possibilities with the new EBS machine, which is just starting to run at the ESRF: “It will improve resolution, the limits of detection of trace elements and provide us with an even more stable beam, so I am really looking forward to using it”, he concludes.

Reference:

Laurence Lemelle, L., et al,  Communications Biology, 09 July 2020. DOI : 10.1038/s42003-020-1084-0

Text by Montserrat Capellas Espuny

 

Top image: Composition of P/Fe/S in a section of a neuron of the substantia nigra. The neuron and its nucleus are highlighted by dashed lines. Cytoplasmic granules rich in Fe and S are pointed out by arrows. Credits: Lemelle, L, et al, Communications Biology, DOI : 10.1038/s42003-020-1084-0.