Ultrastructural abnormalities of myelinated fibres in the peripheral nerves of streptozotocin induced diabetic rats and genetically diabetic (db/db) mice
Qualitative and quantitative ultrastructural observations have been made on myelinated fibres in the tibial and medial plantar nerves of genetically diabetic C57/BL/Ks(db/db) and age-matched nondiabetic (m/m) control mice at 9 and 15 months of age. The cross sectional area of myelinated fibres and their axons in both nerves was found to be significantly less in diabetic mice when compared with age-matched controls. No age related decrease in axon or fibre size was noted in the diabetic at either site. The number of myelin lamellae was found to be proportionate for axon size in the tibial nerve. In the medial plantar nerve regenerated and remyelinated fibres were frequently encountered in both diabetic and age-matched controls, but were more numerous in some fascicles of diabetic animals. The morphometric data from this site was more complex, plottings of myelin area against axonal area showed a greater scatter in the 15 months diabetic group, reflecting the heterogeneity of the fibre population at this site. Plotting g ratio against axon diameter provided a rather neat way of breaking the fibre population into its component parts. The index of circularity of myelinated axons did not differ between diabetic and control animals at 15 months in the tibial nerve. However, in the plantar nerve mean axonal index of circularity was found to be significantly less in diabetic mice when compared with age-matched controls at 9 and 15 months. Axonal glycogenosomes, polyglucosan bodies, axonal compartmentalisation by Schwann cell processes and Pi granules of Reich were assessed for diabetic and control mice at both sites. Only axonal glycogenosomes were significantly more numerous in the diabetic groups. The absence of a selective reduction of axonal size in the tibial nerve in the diabetic mice did not favour a primary axonopathy. As growth in tibial bone length was reduced in these mice the reduction in fibre calibre may be due to a maturational deficit; ultrastructural abnormalities in the medial plantar nerve may suggest a pressure type neuropathy. Male Sprague Dawley rats aged 20 - 21 weeks were made diabetic with streptozotocin and maintained for 2, 4 and 6 months. Myelinated fibre area increased significantly in the tibial nerve of controls over the period of study. Fibre area in the diabetic animals was significantly less than age-matched controls at 4 and 6 months but not less than onset. Axonal perimeter was found to be significantly less in diabetic animals at 2 and 6 months when compared with age-matched controls. No significant difference was detected in the cross sectional area of axons between diabetic and age-matched controls at 2 and 4 months but was significantly less in the diabetic animals at 6 months as compared with age-matched controls (P 0.05). There was no significant difference in axonal index of circularity between diabetic and age-matched controls at 4 and 6 months, mean axonal index of circularity was significantly greater in the diabetic nerves at 2 months when compared with age-matched controls. With regard to myelin sheath thickness, the number of myelin lamellae was related in various ways to axonal dimensions. The highest correlation was found when cross sectional axonal area was related to myelin area, which was estimated from number of myelin lamellae and periodicity. Regression analysis revealed that the slope for control nerves was significantly steeper than diabetics at 4 and 6 months, suggesting a greater effect on myelin area. Myelin area estimates were significantly less in diabetic at 2, 4 and 6 months when compared with age-matched controls, but not less than onset. There was no significant difference in the incidence of the various organelles between diabetic and age-matched controls at any survival period. However, there was a border line increase in axonal glycogenosomes in the diabetics at 6 months. This study may suggest that there is a maturational deficit in nerve fibre size and myelination in streptozotocin induced diabetes in the rat.