Silver diagnosis in neuropathology: principles, practice and revised interpretation

Silver-staining methods are helpful for histological identification of pathological deposits. In spite of some ambiguities regarding their mechanism and interpretation, they are widely used for histopathological diagnosis. In this review, four major silver-staining methods, modified Bielschowsky, Bodian, Gallyas (GAL) and Campbell–Switzer (CS) methods, are outlined with respect to their principles, basic protocols and interpretations, thereby providing neuropathologists, technicians and neuroscientists with a common basis for comparing findings and identifying the issues that still need to be clarified. Some consider “argyrophilia” to be a homogeneous phenomenon irrespective of the lesion and the method. Thus, they seek to explain the differences among the methods by pointing to their different sensitivities in detecting lesions (quantitative difference). Comparative studies, however, have demonstrated that argyrophilia is heterogeneous and dependent not only on the method but also on the lesion (qualitative difference). Each staining method has its own lesion-dependent specificity and, within this specificity, its own sensitivity. This “method- and lesion-dependent” nature of argyrophilia enables operational sorting of disease-specific lesions based on their silver-staining profiles, which may potentially represent some disease-specific aspects. Furthermore, comparisons between immunohistochemical and biochemical data have revealed an empirical correlation between GAL+/CS-deposits and 4-repeat (4R) tau (corticobasal degeneration, progressive supranuclear palsy and argyrophilic grains) and its complementary reversal between GAL-/CS+deposits and 3-repeat (3R) tau (Pick bodies). Deposits containing both 3R and 4R tau (neurofibrillary tangles of Alzheimer type) are GAL+/CS+. Although no molecular explanations, other than these empiric correlations, are currently available, these distinctive features, especially when combined with immunohistochemistry, are useful because silver-staining methods and immunoreactions are complementary to each other

Protein synthesis and transport in the regenerating goldfish visual system

The nature of the proteins synthesized in the goldfish retina and axonally transported to the tectum during optic nerve regeneration has been examined. Electrophoretic analysis of labeled soluble retinal proteins by fluorography verified our previous observation of a greatly enhanced synthesis of the microtubule subunits. In addition, labeling of a tubulin-like protein in the retinal particulate fraction was also increased during regeneration. Like soluble tubulin, the particulate material had an apparent MW of 53–55K and could be tyrosylated in the presence of cycloheximide and [ 3 H]tyrosine. Comparison of post-crush and normal retinal proteins by two-dimensional gel electrophoresis also revealed a marked enhancement in the labeling of two acidic 68–70K proteins. Analysis of proteins slowly transported to the optic tectum revealed changes following nerve crush similar to those observed in the retina, with enhanced labeling of both soluble and particulate tubulin and of 68–70K polypeptides. The most striking change in the profile of rapidly transported protein was the appearance of a labeled 45K protein which was barely detectable in control fish.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45430/1/11064_2004_Article_BF00965529.pd

Experimental diabetic neuropathy: impairment of slow transport with changes in axon cross-sectional area.

Analysis of slow axonal transport in the sciatic and primary visual systems of rats with streptozotocin-induced diabetes of 4-6 weeks duration showed impairment of the transport of neurofilament subunits, tubulin, actin, and a 30- and a 60-kDa polypeptide in both systems. The degree of impairment was not uniform. Transport of polypeptide constituents of the slow component b, such as the 30- and 60-kDa polypeptides, appeared to be more severely affected than the transport of constituents of the slow component a, such as neurofilaments. Morphometric analysis of sciatic axons revealed a proximal increase and a distal decrease of axonal cross-sectional area. It is proposed that impairment of axoplasmic transport and changes of axonal size are related. Transport impairment results in a larger number of neurofilaments, microtubules, and other polypeptides in the proximal region of the axon, which increases in size, whereas fewer neurofilaments, microtubules, and other polypeptides reach the distal axons that show a size decrease. Such changes in axonal transport and area are likely to occur in other diabetic animal models and in human diabetes

Chemical neurotoxins accelerating axonal transport of neurofilaments.

no abstract availabl