Synchrotron radiation-based FTIR spectro-microscopy of the brainstem of the hSOD1 G93A rat model of amyotrophic lateral sclerosis

Autor:	Tanja Dučić, Pavle R. Andjus, Stefan Stamenković
Rok vydání:	2019
Předmět:	0301 basic medicine 030103 biophysics SOD1 Biophysics Mice Transgenic Protein aggregation Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound Superoxide Dismutase-1 Spectroscopy Fourier Transform Infrared medicine Animals Humans Choline Amyotrophic lateral sclerosis Microscopy biology Gigantocellular reticular nucleus Chemistry Amyotrophic Lateral Sclerosis General Medicine medicine.disease Molecular biology Rats Disease Models Animal 030104 developmental biology Trigeminal motor nucleus medicine.anatomical_structure Mutation biology.protein Brainstem Synchrotrons Brain Stem
Zdroj:	European Biophysics Journal. 48:475-484
ISSN:	1432-1017 0175-7571
DOI:	10.1007/s00249-019-01380-5
Popis:	Pathological mechanisms in amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disease, are still poorly understood. One subset of familial ALS cases is caused by mutations in the metallo-enzyme copper-zinc superoxide dismutase (SOD1), increasing the susceptibility of the SOD1 protein to form insoluble intracellular aggregates. Here, we employed synchrotron radiation-based Fourier transform infrared spectroscopy and microscopy to investigate brainstem cross-sections from the transgenic hSOD1 G93A rat model of ALS that overexpresses human-mutated SOD1. We compared the biomacromolecular organic composition in brainstem tissue cross-sections of ALS rats and their non-transgenic littermates (NTg). We demonstrate that the proteins and especially their antiparallel β-sheet structure significantly differed in all three regions: the facial nucleus (FN), the gigantocellular reticular nucleus (GRN) and the trigeminal motor nucleus (TMN) in the brainstem tissue of ALS rats. The protein levels varied between different brainstem areas, with the highest concentration observed in the region of the FN in the brainstem tissue of NTg animals. Furthermore, the concentration of lipids and esters was significantly decreased in the TMN and FN of ALS animals. A similar pattern was detected for choline and phosphate assigned to nucleic acids with the highest concentrations in the FN of NTg animals. The spectroscopic analysis showed significant differences in phosphates, amide and lipid structure in the FN of NTg animals in comparison with the same area of ALS rats. These results show that the hG93A SOD1 mutation causes metabolic cellular changes and point to a link between bioorganic composition and hallmarks of protein aggregation.
Databáze:	OpenAIRE
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