Ultrastructural studies of the dying-back process II. The sequestration and removal by Schwann cells and oligodendrocytes of organelles from normal and diseased axons
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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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