X-Ray Microscopy for Neuroscience: Novel Opportunities by Coherent Optics

Salditt, Tim; Dučić, Tanja

doi:10.1007/978-1-62703-983-3_11

Cited by 9 publications

(8 citation statements)

References 103 publications

(157 reference statements)

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“…Significant instrumentation improvements in the past decade led to the development of synchrotron-based methods that allow determination of the intracellular distribution of different elements as well as the chemical groups. 32,47,48 Protein aggregation and the formation of intracellular inclusions is a central feature of many neurodegenerative disorders, but the precise knowledge about their pathophysiological involvement is lacking. In this study we applied multimodal cellular synchrotron-based methods to elucidate the intracellular alterations occurring in astrocytes of the ALS animal model that overexpresses G93A mutated hSOD1.…”

Section: ■ Discussionmentioning

confidence: 99%

Multimodal Synchrotron Radiation Microscopy of Intact Astrocytes from the hSOD1 G93A Rat Model of Amyotrophic Lateral Sclerosis

et al. 2018

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Amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, is the most common adult onset neurodegenerative disorder affecting motor neurons. Disruptions in metal ion homeostasis have been described in association with ALS, but the pathological mechanisms are still poorly understood. One of the familial ALS cases is caused by mutations in the metallo-enzyme copper–zinc superoxide dismutase (SOD1). In this study, we employed orthogonal cellular synchrotron radiation based spectro-microscopies to investigate the astrocytes of an ALS animal model: the rat hSOD1 G93A that overexpresses human mutated SOD1, which is known to increase the susceptibility of the SOD1 protein to form insoluble intracellular aggregates. Specifically, we applied soft X-ray transmission tomography and hard X-ray fluorescence microscopy in situ, Fourier transform infrared spectro-microscopy to detect and analyze aggregates, as well as to determine the alterations in the cellular ultrastructure and the elemental and the organic composition of ALS model astrocytes with respect to the control astrocytes isolated from nontransgenic littermates (NTg). The present study demonstrates that large aggregates in the form of multivesicular inclusions form exclusively in the ALS model astrocytes and not in the NTg counterpart. Furthermore, the number of mitochondria, the cellular copper concentration, and the amount of antiparallel β-sheet structures were significantly changed within the cells of the ALS model as well as the lipid localization and composition. Also, our data indicate that choline was decreased in the ALS model astrocytes, which could explain their higher sensitivity to oxidative stress that we observed. These results show that the hG93A SOD1 mutation causes metabolic and ultrastructural cellular changes and point to a link between an increased copper concentration and aggregation: the most probable that the aggregation of G93A hSOD1 may perturb its binding to Cu, thus directly or indirectly affecting Cu homeostasis.

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Section: ■ Discussionmentioning

confidence: 99%

Multimodal Synchrotron Radiation Microscopy of Intact Astrocytes from the hSOD1 G93A Rat Model of Amyotrophic Lateral Sclerosis

et al. 2018

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“…By automated analysis, 2D maps of x-ray fluorescence (XRF) and diffraction signals can then be generated, providing advanced contrast mechanisms of scanning transmission x-ray microscopy (STXM). STXM with XRF contrast [14] has already become a fairly well established method for trace element mapping in neural cells and tissues, as reviewed in [15] and in [16]. In contrast to electron microscopy based x-ray microanalysis (EDX), XRF collects signal from the interior of the tissue section, with a sensitivity down to a few hundred atoms of an element in a pixel, and can also be used for speciation.…”

Section: Introductionmentioning

confidence: 99%

Imaging of neuronal tissues by x-ray diffraction and x-ray fluorescence microscopy: evaluation of contrast and biomarkers for neurodegenerative diseases

Carboni

Nicolas

Töpperwien

et al. 2017

Biomed. Opt. Express

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We have used scanning X-ray diffraction (XRD) and X-ray fluorescence (XRF) with micro-focused synchrotron radiation to study histological sections from human substantia nigra (SN). Both XRF and XRD mappings visualize tissue properties, which are inaccessible by conventional microscopy and histology. We propose to use these advanced tools to characterize neuronal tissue in neurodegeneration, in particular in Parkinson's disease (PD). To this end, we take advantage of the recent experimental progress in x-ray focusing, detection, and use automated data analysis scripts to enable quantitative analysis of large field of views. XRD signals are recorded and analyzed both in the regime of small-angle (SAXS) and wide-angle x-ray scattering (WAXS). The SAXS signal was analyzed in view of the local myelin structure, while WAXS was used to identify crystalline deposits. PD tissue scans exhibited increased amounts of crystallized cholesterol. The XRF analysis showed increased amounts of iron and decreased amounts of copper in the PD tissue compared to the control.

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“…The novel opportunities of highly focused synchrotron radiation for FTIR and XRF can be used to study the local chemical structure in a single cell without any staining, labeling or cutting artifacts (reviewed in ref. [23]). As the resolution of each imaging technique differs, the pixel size for the XRF and FTIR imaging were different in this study, i.e.…”

Section: Introductionmentioning

confidence: 99%

Lipids status and copper in a single astrocyte of the rat model for amyotrophic lateral sclerosis: Correlative synchrotron‐based X‐ray and infrared imaging

Kreuzer

Stamenković

Chen

et al. 2020

Journal of Biophotonics

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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease, causing death of motor neurons controlling voluntary muscles. The pathological mechanisms of the disease are only partially understood. The hSOD1-G93A ALS rat model is characterized by an overexpression of human mutated SOD1, causing increased vulnerability by forming intracellular protein aggregates, inducing excitotoxicity, affecting oxidative balance and disturbing axonal transport. In this study we followed the bio-macromolecular organic composition and compartmentalization together with trace metal distribution in situ in single astrocytes from the ALS rat model and compared them to the control astrocytes from nontransgenic littermates by simultaneous use of two synchrotron radiation-based methods: Fourier transform infrared microspectroscopy (SR-FTIR) and hard Xray fluorescence microscopy (XRF). We show that ALS cells contained more Cu, which colocalized with total lipids, increased carbonyl groups and oxidized lipids, thus implying direct involvement of Cu in oxidative stress of lipidic components without direct connection to protein aggregation in situ.

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X-Ray Microscopy for Neuroscience: Novel Opportunities by Coherent Optics

Cited by 9 publications

References 103 publications

Multimodal Synchrotron Radiation Microscopy of Intact Astrocytes from the hSOD1 G93A Rat Model of Amyotrophic Lateral Sclerosis

Multimodal Synchrotron Radiation Microscopy of Intact Astrocytes from the hSOD1 G93A Rat Model of Amyotrophic Lateral Sclerosis

Imaging of neuronal tissues by x-ray diffraction and x-ray fluorescence microscopy: evaluation of contrast and biomarkers for neurodegenerative diseases

Lipids status and copper in a single astrocyte of the rat model for amyotrophic lateral sclerosis: Correlative synchrotron‐based X‐ray and infrared imaging

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