Metabolic relationships between proteins of myelin and paranodally shedded, partially degraded myelin fragments in the rabbit CNS

Abstract

The "close-to-node" regions of myelinated nerve fibres, i.e., the paranodal end segments, are generally thought to be sites of high metabolic activity and myelin sheath turnover. Data on turnover rates of individual myelin constituents are conflicting but there exists a common belief that myelin is metabolized as independent molecules rather than as a unit. The occurrence of paranodal Marchi-positive bodies, with morphological and biochemical properties consistent with partially degraded myelin, prompted us to examine the temporal dynamics of the incorporation of radioactive precursor label in the major proteins of myelin and the Marchi-positive bodies. 3H-leucine was administered intrathecally in adult rabbits. After various survival times, the spinal cord was subfractionated by ultracentrifugation in a discontinuous two-step 0.32 M/0.85 M sucrose gradient. Myelin was collected from the interface and a floating fraction, heavily enriched in Marchi-positive bodies, was recovered on top of the 0.32 M sucrose. By scintillation counting and by gel fluorography combined with immunoblotting, a gradual appearance with time of partially degraded peptides of myelin-associated protein and 2',3'-cyclic nucleotide 3'-phosphodiesterase was seen in the floating fraction but not in myelin. The temporal dynamics of the specific activities of these two proteins and myelin-basic protein and proteolipid protein were consistent with a typical source-product relationship between myelin and the material in the floating fraction. In conjunction with earlier morphological and biochemical findings, these data may suggest that Marchi-positive bodies appear as a consequence of myelin catabolism.

Mitochondrial dynamics and bioenergetics regulated by netrin‐1 in oligodendrocytes

“…In contrast, the number of mitochondria estimated in larger Schwann cell paranodal loops ranges from a few hundreds to thousands per node (Rydmark, Berthold, & Gatzinsky, 1998). Past studies argued that CNS paranodal loops lack mitochondria (Corneliuson, Berthold, Fabricius, Gatzinsky, & Carlstedt, 1989;Hildebrand, 1971;Persson, Berthold, Rydmark, & Fabricius, 1992), but recent findings (Rinholm et al, 2016) and the present study suggest that mitochondria may be recruited by signaling at CNS paranodal junctions.…”

Activation of calpain‐1 in myelin and microglia in the white matter of the aged rhesus monkey

“…2003) and in brain stem myelin, as demonstrated in the present study. Using metabolic labeling studies, degraded myelin proteins originally found in the intact fraction can be demonstrated within the floating fraction (Persson 1991; Persson and Karlsson 1991; Persson et al . 1992).…”

Age‐dependent myelin degeneration and proteolysis of oligodendrocyte proteins is associated with the activation of calpain‐1 in the rhesus monkey

“…Isolation of myelin fractions from brain white matter revealed that the protein content of the floating myelin fraction, which has been shown to contain degraded myelin protein (Persson and Corneliuson 1989; Persson and Karlsson 1991; Persson et al . 1992), increased with age.…”

“…Isolation of myelin fractions from brain white matter revealed that the protein content of the floating myelin fraction, which has been shown to contain degraded myelin protein (Persson and Corneliuson 1989;Persson and Karlsson 1991;Persson et al 1992), increased with age. In addition to aging, it is noteworthy that increased amounts of floating myelin have been demonstrated in inflammatory and demyelinating diseases of brain white matter, perhaps as a result of inflammatory injury to the myelin membrane (Norton and Cammer 1984b).…”

“…Metabolic labeling of myelin indicates that specific incorporation proceeds from the intact myelin fraction to the floating myelin fraction (Persson and Corneliuson 1989). This floating fraction has been shown to contain degraded myelin proteins, which appear to be derived from the metabolic or pathologic breakdown of myelin proteins contained in the intact myelin fraction (Persson 1991; Persson and Karlsson 1991; Persson et al 1992).…”