Visualization of the Breakdown of the Axonal Transport Machinery: a Comparative Ultrastructural and Immunohistochemical Approach

Molecular Neurobiology
Sebastian RühlingTanja Hochstrasser

Abstract

Axonal damage is a major factor contributing to disease progression in multiple sclerosis (MS) patients. On the histological level, acute axonal injury is most frequently analyzed by anti-amyloid precursor protein immunohistochemistry. To what extent this method truly detects axonal injury, and whether other proteins and organelles are as well subjected to axonal transport deficits in demyelinated tissues is not known. The aim of this study was to correlate ultrastructural morphology with the immunohistochemical appearance of acute axonal injury in a model of toxin-induced oligodendrocyte degeneration. C57BL/6J mice were intoxicated with 0.25% cuprizone to induce demyelination. The corpus callosum was investigated by serial block-face scanning electron microscopy (i.e., 3D EM), immunohistochemistry, and immunofluorescence microscopy. Brain tissues of progressive MS patients were included to test the relevance of our findings in mice for MS. Volumes of axonal swellings, determined by 3D EM, were comparable to volumes of axonal spheroids, determined by anti-APP immunofluorescence stains. Axonal swellings were present at myelinated and non-myelinated axonal internodes. Densities of amyloid precursor protein (APP)+ spheroids were h...Continue Reading

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Methods Mentioned

BETA
scanning electron microscopy
electron microscopy

Key Resources (RRID) Mentioned

AB_2237198
AB_2665520
AB_304558
AB_94882
AB_443084
AB_445559
AB_10710315
AB_2637258
AB_2057371
AB_10979984

Software Mentioned

GraphPad
GraphPad Prism
Neurolucida Explorer
Reconstruct
Stereo Investigator
ImageJ
BioVis3D
Neurolucida360

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