Immunohistochemical Features of Dystrophic Axons in Papillon Dogs with Neuroaxonal Dystrophy

The immunohistochemical features of dystrophic axons in brain tissues of Papillon dogs with neuroaxonal dystrophy (NAD) were examined in comparison with 1 dog with cerebellar cortical abiotrophy (CCA) and a dog without neurologic signs. Histologically, many dystrophic axons were observed throughout the central nervous system of all dogs with NAD. These axonal changes were absent in the dog with CCA and in the control dog. Severe Purkinje cell loss was found in the dog with CCA, whereas the lesions were milder in all dogs with NAD. Immunohistochemically, the many dystrophic axons were positive for neurofilaments, tau, α/β-synuclein, HSP70, ubiquitin, synaptophysin, syntaxin-1, and synaptosomal-associated protein-25 (SNAP-25). A few dystrophic axons were positive for α-synuclein. In addition, these dystrophic axons, especially in the nucleus gracilis, cuneatus, olivaris, and spinal tract of the trigeminal nerve, were intensely immunopositive for the 3 calcium-binding proteins calretinin, calbindin, and parvalbumin. The accumulation of synapse-associated proteins in the dystrophic axons may indicate dysfunction of the synapse at the presynaptic portion. The accumulation of α-synuclein in the dystrophic axon and region-specific appearance of calcium-binding protein-positive spheroids are considered as unique features in NAD of Papillon dogs, providing the key to elucidate the pathogenesis.

Organization of the axolemma in amyelinated axons: a cytochemical study in dy/dy dystrophic mice

Previous studies using a variety of techniques have shown that in normal myelinated fibres there are structural differences between the axon membrane at nodes of Ranvier and in the internodes beneath the myelin sheath. The present paper reports the results of a cytochemical study on the axon membrane in amyelinated axons in dy/dy dystrophic mice, in which myelination is focally absent owing to a genetic defect. The results indicate that the amyelinated axon membrane, which is known to be capable of sustaining continuous impulse conduction, is structurally different from normal nodal membrane. Comparison of the cytochemical results with physiological and pharmacological data suggests that the amyelinated dystrophic axon membrane may exhibit a lower sodium channel density than normal nodal membrane.