Summary
A mechanism is postulated and described for the sequestration and phagocytosis of unusual and abnormal axoplasmic organelles by Schwann and oligodendroglial cells. Axonal organelles involved in this process are clear and dense-core vesicles, membrane-bounded dense membranous bodies reminiscent of secondary lysosomes, enlarged mitochondria, glycogen-like granules and glycogen-filled mitochondrial remnants. The process of sequestration of these organelles begins with the formation of a ridge of ensheathing cell adaxonal cytoplasm adjacent to an internally coated region of axolemma. The ridge of adaxonal cytoplasm enlarges to form a thin sheet which indents the axon surface adjacent to the abnormal axonal organelles. The invaginating adaxonal cytoplasmic sheet surrounds the abnormal axonal organelles and segregates them from the remainder of the axon. The cytoplasmic sheet infolds on itself and sequesters groups of axoplasmic organelles to form an interdigitated profile when viewed in cross-section. Electron lucent areas correspond to sequestered axoplasm and electron dense areas to ensheathing cell cytoplasm. The membranes separating axoplasm and ensheathing cell cytoplasm in the interdigitated networks break down allowing the abnormal axoplasmic organelles to be phagocytosed by the ensheathing cell cytoplasm. The process occurs to a limited degree in the normal nervous system at paranodes but is much more developed in pathologic situations where there is early axonal disease. The process is maximally developed in situations where there is centripetal axonal degeneration such as occurs in dying-back toxic disease and in the proximal stump of an amputated nerve.
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The authors wish to thank Drs E. Holtzman, H. H. Schaumburg and W. Schlaepfer for discussion, Drs C. S. Raine and R. D. Terry for support, and Ann Armstrong, Miriam Pakingan, Howard Finch and Everett Swanson for excellent technical assistance. Joy Zagoren and Nelson Tesser kindly assisted with the preparation of Fig. 30. This study was supported in part by USPHS grant NS 08952, and grants from the Alfred P. Sloan Foundation, the Muscular Dystrophy Group of Great Britain and Eastman Kodak Company, New York. Dr Spencer is the recipient of a Joseph P. Kennedy, Jr, Fellowship in the Neurosciences.
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Spencer, P.S., Thomas, P.K. Ultrastructural studies of the dying-back process II. The sequestration and removal by Schwann cells and oligodendrocytes of organelles from normal and diseased axons. J Neurocytol 3, 763–783 (1974). https://doi.org/10.1007/BF01097197
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DOI: https://doi.org/10.1007/BF01097197