Progressive axonopathy: An inherited neuropathy of boxer dogs. 4. myelin sheath and Schwann cell changes in the nerve roots

Abstract

Changes in the myelin sheath have been studied in the nerve roots of dogs with Progressive axonopathy, an autosomal recessive inherited neuropathy. The earliest changes were attenuation of the sheath at the proximal paranode and adjacent internode, probably in response to the axonal swelling which occurs in this area. Myelin bubbles were frequently observed along internodes. As the disease developed, progressively more fibres demonstrated short internodes of irregular length and thin myelin sheaths suggesting extensive remyelination and remodelling of the sheath. Short lengths of axons devoid of myelin, and occasional macrophages were also encountered. Sheaths of both original and newly formed internodes were highly irregular in outline. Occasional intra-axonal projections of adaxonal Schwann cell cytoplasm were observed, but complex interdigitations were unusual. A moderately electron-dense, granular material accumulated within the myelin sheath, becoming more obvious in the advanced disease. This material of unknown origin and composition was located predominantly at the intraperiod line principally between the adaxonal cytoplasm and the inner major dense line, but also at Schmidt-Lanterman incisures and between paranodal loops. Xenografts of the canine nerves into athymic mice failed to demonstrate any of the myelin sheath changes. The temporal and spatial relationship of the myelin sheath and axonal changes and the failure to reproduce the natural lesion in grafts suggest that Schwann cell alterations probably occur in response to the axonal changes.