Summary
Nodal and paranodal regions of myelinated sciatic nerve fibres from diabetic (db/db) mice were examined in freeze fracture replicas. In some fibres, the axolemma was found to display abnormalities in the paranodal region. These include shallow, undifferentiated junctional indentations, thinning of the indentations with widening of the non-junctional grooves between them, particle clusters within the non-junctional grooves, and patches in which axolemmal E-face particles are distributed randomly rather than in the form of linear strings within grooves. Nodal structure, in contrast, is hardly affected. Nodal E-face and P-face particle densities indb/db axons are not significantly different from those in age-matched controls, although we found a few examples in which the E-face density fell slightly below the normal range. Occasional fibres showing evidence of paranodal or segmental demyelination were also seen. The results support paranodal pathology as a potential basis for reduced nerve conduction velocity in diabetic nerves but provide no evidence for significant changes in nodal structure or in nodal Na channel density in sciatic nerve fibres of thedb/db mouse.
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Black, J. A., Waxman, S. G. &Hildebrand, C. (1984) Membrane specialization and axo-glial association in the rat retinal nerve fibre layer: freeze-fracture observations.Journal of Neurocytology 13, 417–30.
Black, J. A., Waxman, S. G. &Smith, M. E. (1987) Macromolecular structure of axonal membrane during acute experimental allergic encephalomyelitis in rat and guinea pig spinal cord.Journal of Neuropathology and Experimental Neurology 46, 167–84.
Blank, W. F., Bunge, M. B. &Bunge, R. P. (1974) The sensitivity of the myelin sheath, particularly the Schwann cell-axolemmal junction, to lowered calcium levels in cultured sensory ganglia.Brain Research 67, 503–18.
Bostock, H. &Sears, T. A. (1978) The internodal axon membrane: electrical excitability and continuous conduction in segmental demyelination.Journal of Physiology 280, 273–301.
Brismar, T., Anders, A. &Sima, A. A. F. (1981) Changes in nodal function in nerve fibres of the spontaneously diabetic BB-Wistar rat: potential clamp analysis.Acta Physiologica Scandinavica 113, 499–506.
Dyck, P. J., Lambert, E. H., Windebank, A. J., Lois, A. A., Sparks, M. F., Karnes, J., Sherman, W. R., Hallcher, L. M., Low, P. A. &Service, J. F. (1981) Acute hyperosmolar hyperglycemia causes axonal shrinkage and reduced nerve conduction velocity.Experimental Neurology 71, 507–14.
Greene, D. A., Chakravarti, S., Lattimer, S. A. &Sima, A. A. F. (1987) Role of sorbitol accumulation and myoinositol depletion in paranodal swelling of large myelinated nerve fibres in the insulin-deficient spontaneous diabetic bio-breeding rat.Journal of Clinical Investigation 79, 1479–85.
Greene, D. A. &Lattimer, S. A. (1984) Action of sorbinil in diabetic peripheral nerve. Relationship of polyol (sorbitol) pathway inhibition to a myo-inositol-mediated defect in sodium-potassium ATPase activity.Diabetes 33, 712–16.
Greene, D. A., Yagihashi, S., Lattimer, S. A. &Sima, A. A. F. (1984) Nerve Na+-K+ ATPase, conduction, and myo-inositol in the insulin-deficient BB rat.American Journal of Physiology 247, E534–9.
Hasegawa, M., Rosenbluth, J. &Ishise, J. (1988) Nodal and paranodal structural changes in mouse and rat optic nerve during Wallerian degeneration.Brain Research 452, 345–57.
Hirano, A. &Dembitzer, H. M. (1982) Further studies on the transverse bands.Journal of Neurocytology 11, 851–6.
Ishise, J. &Rosenbluth, J. (1986) Nodal and paranodal structural changes in frog optic nerve during early Wallerian degeneration.Journal of Neurocytology 15, 657–70.
LaFontaine, S., Rasminsky, M., Saida, T. &Sumner, A. (1982) Conduction block in rat myelinated fibres following acute exposure to anti-galactocerebroside serum.Journal of Physiology 323, 287–306.
Moore, S. A., Peterson, R. G., Felten, D. L., Cartwright, T. R. &O'Connor, B. L. (1980) Reduced sensory and motor conduction velocity in 25-week-old diabetic [C57BL/Ks(db/db)] mice.Experimental Neurology 70, 548–55.
Norido, F., Canella, R., Zanoni, R. &Gorio, A. (1984) Development of diabetic neuropathy in the C57BL/Ks(db/db) mouse and its treatment with gangliosides.Experimental Neurology 83, 221–32.
Robertson, D. M. &Sima, A. A. F. (1980) Diabetic neuropathy in the mutant mouse [C57BL/Ks(db/db)], a morphometric study.Diabetes 29, 60–7.
Rosenbluth, J. (1976) Intramembranous particle distribution at the node of Ranvier and adjacent axolemma in myelinated axons of the frog brain.Journal of Neurocytology 5, 731–45.
Rosenbluth, J. (1981) Freeze-fracture approaches to ionophore localization in normal and myelin-deficient nerves. InDemyelinating Disease: Basic and Clinical Electrophysiology (edited byWaxman, S. G. &Ritchie, J. M.),Advances in Neurology 31, 391–418. New York: Raven Press.
Rosenbluth, J. (1983) Intramembranous particle distribution in nerve fibre membranes.Experientia 39, 953–63.
Rosenbluth, J. (1984) Membranous specializations at the nodes of Ranvier and paranodal and juxtaparanodal regions of myelinated central and peripheral nerve fibers. InThe node of Ranvier (edited byZagoren, J. C. &Fedoroff, S.), pp. 31–67. Orlando: Academic Press.
Rosenbluth, J. (1988) Role of glial cells in the differentiation and function of myelinated axons.International Journal of Developmental Neuroscience 6, 3–24.
Rosenbluth, J., Sumner, A. J. &Saida, T. (1981) Dedifferentiation of the axolemma associated with demyelination. InProceedings of the 39th EMSA Meeting (edited byBailey, G. W.), pp. 496–7. Baton Rouge: Claitor's.
Rosenbluth, J., Tao-Cheng, J.-H. &Blakemore, W. F. (1985) Dependence of axolemmal differentiation on contact with glial cells in chronically demyelinated lesions of the cat spinal cord.Brain Research 358, 287–302.
Schiavinato, A., Morandin, A. &Gorio, A. (1985) Quantitative analysis of myelin and axolemma particle distribution in C57BL/Ks diabetic mice and the effects of ganglioside treatment.Journal of the Neurological Sciences 69, 301–17.
Sharma, A. K., Thomas, P. K., Gabriel, G., Stolinski, C., Dockery, P. &Hollins, G. W. (1983) Peripheral nerve abnormalities in the diabetic mutant mouse.Diabetes 32, 1152–61.
Sima, A. A. F. &Brismar, T. (1985) Reversible diabetic nerve dysfunction: structural correlates to electrophysiological abnormalities.Annals of Neurology 18, 21–9.
Sima, A. A. F., Lattimer, S. A., Yagihashi, S. &Greene, D. A. (1986) Axo-glial dysjunction, a novel structural lesion that accounts for poorly reversible slowing of nerve conduction in the spontaneous diabetic Bio-Breeding rat.Journal of Clinical Investigation 77, 474–84.
Sima, A. A. F. &Robertson, D. M. (1978) Peripheral neuropathy in mutant diabetic mouse [C57BL/Ks(db/db)].Acta Neuropathologica (Berlin) 41, 85–9.
Smith, K. J. &McDonald, W. I. (1982) Spontaneous and evoked electrical discharges from a central demyelinating lesion.Journal of the Neurological Sciences 55, 39–47.
Tao-Cheng, J.-H. &Rosenbluth, J. (1982) Development of nodal and paranodal membrane specializations in amphibian peripheral nerves.Developmental Brain Research 3, 577–94.
Tao-Cheng, J.-H. &Rosenbluth, J. (1984) Extranodal particle accumulations in the axolemma of myelinated frog optic axons.Brain Research 308, 289–300.
Thomas, P. K. &Elliasson, S. G. (1984) Diabetic neuropathy. InPeripheral Neuropathy (edited byDyck, P. J., Thomas, P. K., Lambert, E. H. &Bunge, R.), 2nd Edition, pp. 1773–810. Philadelphia: W. B. Saunders.
Thomas, P. K. &Lascelles, R. G. (1966) The pathology of diabetic neuropathy.Quarterly Journal of Medicine 35, 489–509.
Waxman, S. G. &Ritchie, J. M. (1985) Organization of ion channels in the myelinated nerve fibre.Science 228, 1502–7.
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Shirasaki, N., Rosenbluth, J. Structural abnormalities in freeze-fractured sciatic nerve fibres of diabetic mice. J Neurocytol 20, 573–584 (1991). https://doi.org/10.1007/BF01215265
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DOI: https://doi.org/10.1007/BF01215265