Wallerian Degeneration in the Rat a Chemical Study

Apolipoprotein E is synthesized and secreted by rat sciatic nerve consequent to several types of injury. It has been proposed that endoneurial apolipoprotein E, in analogy to its role in systemic cholesterol transport, is involved in the salvage and reutilization of myelin cholesterol during degeneration and regeneration. To test this hypothesis, nerve lipids were prelabeled via intraneural injection of [3H]acetate. Four weeks later the nerves were crushed. From 1 to 12 weeks later, crushed nerves were examined for extracellular lipoprotein-bound cholesterol label. By 2 weeks after injury, 10% of the endoneurial lipid label was in a soluble form that was releasable into incubation medium. This released fraction was enriched in labeled cholesterol, and its labeled lipid composition was constant, in contrast to the changing distribution of label in the nerve with time after injury. On a KBr gradient, the released lipid label cofractionated with the released apolipoprotein E at densities similar to that of lipoproteins. These data indicate that at least some myelin cholesterol in injured nerve becomes associated with apolipoprotein E-containing lipoproteins and thus is available for reutilization via the hypothesized model.

Section: Discussionmentioning

confidence: 68%

mentioning

confidence: 99%

Cholesterol from Degenerating Nerve Myelin Becomes Associated with Lipoproteins Containing Apolipoprotein E

Goodrum

1991

“…The present studies were undertaken: (1) to see whether cholesterol is retained in the nerve throughout degeneration and regeneration; (2) to ascertain the dynamic role of fatty acids during degeneration and regeneration by an evaluation of fatty acid composition of the nonpolar lipids; (3) to relate the biochemical changes to various pathological stages of nerve fiber degeneration and regeneration; and (4) to provide the basis for comparisons of lipid changes in Wallerian degeneration with those observed in biochemical studies of human neuropathy . Because changes in lipid composition of neural tissue may be masked with analysis of whole nerve (Dyck et al, 1970;Brown et a]., 1979), and increased water content is normally seen in the nerve during Wallerian degeneration (Johnson et al, 1950;Mannel, 1952), our studies were performed with freeze-dried endoneurial distal segments of crushed nerve. Nerves were allowed to regenerate, so that the net effect of varying combinations of degeneration and regeneration could be evaluated together and serially.…”

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confidence: 99%

The Sequential Alterations of Endoneurial Cholesterol and Fatty Acid in Wallerian Degeneration and Regeneration

Yao

Natarajan

Dyck

1980

The endoneurial nonpolar lipids were serially examined throughout Wallerian degeneration and regeneration. Following nerve crush in the rat, the endoneurial content of cholesterol falls and cholesteryl ester content rises dramatically. The maximal alteration of this ratio corresponds reasonably well with events of myelin ovoid dissolution to sudanophilic amorphous lipids. Thereafter, as regenerative events overshadow degenerative events the ratio is slowly restored toward normal. The increased cholesteryl esters are probably synthesized within endoneurium from free fatty acids which become available when myelin is degraded. The endoneurial free fatty acid content presumably represents the net effect of phospholipid degradation, cholesterol esterification, cholesteryl ester hydrolysis, and fascicular entry and exit. Free fatty acids become significantly elevated by 12 days, probably reach a peak between 16 and 60 days, and thereafter return to normal with fiber regeneration. The fatty acid composition of cholesteryl esters from crushed nerves is markedly different from those of normal sciatic nerves. The altered fatty acid composition of cholesteryl esters from myelin suggests that both synthesis and hydrolysis exhibit substrate specificity toward chain length and unsaturation, with oleate being the most favored substrate.

“…Oleate is a substrate for fatty acid chain elongation in brain (see Agranoff, 1989), and such chain elongation presumably accounts for the minor labeling of other fatty acids in nerve . About half the total oleate label was lost during the first 2 weeks following nerve crush, consistent with earlier estimates that the total phospholipid content of nerve decreases by 50% within the first 2 weeks after nerve crush (Johnson et al ., 1949 ;Mannell, 1952;Wood and Dawson, 1974) . The remaining radiolabel in the regenerated nerve was localized in phospholipids and had the same fatty acid distribution as label in uncrushed nerve .…”

Section: The Fate Of [3 H ] Oleatementioning

confidence: 99%

“…It is unknown whether myelin lipids other than cholesterol are degraded locally, transported to the circulation, or reincorporated into myelin . The total content of phospholipids and cerebrosides in sciatic nerve is reported to decrease by -50% within 2 weeks after the onset of Wallerian degeneration (Johnson et al, 1949;Mannell, 1952;Wood and Dawson, 1974), suggesting that significant portions of the phospholipids and cerebrosides are either locally catabolized or transported from the nerve. Consistent with this observation, phospholipase activity is increased during Wallerian degeneration, leading to hydrolysis of phospholipids and production of a pool of free fatty acids (Webster, 1973;Yao et al, 1980) .…”

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confidence: 99%

Fatty Acids from Degenerating Myelin Lipids Are Conserved and Reutilized for Myelin Synthesis During Regeneration in Peripheral Nerve

Goodrum

Weaver

Goines

et al. 1995

Following nerve crush, cholesterol from degenerating myelin is conserved and reutilized for new myelin synthesis during nerve regeneration. The possibility that other myelin lipids are salvaged and reutilized has not been investigated previously. We examined the fate of myelin phospholipids and their fatty acyl moieties following nerve crush by electron microscopic autoradiography of myelin lipids prelabeled with [3H]oleate or [2‐3H]‐glycerol. Both precursors were incorporated predominantly (>90%) into phospholipids; >85% of the [3H]oleate was incorporated as oleate, with the remainder in longer‐chain fatty acids. Before nerve crush, both labels were restricted to myelin sheaths. Following nerve crush and subsequent regeneration, over half the label from [3H]oleate, but little from [2‐3H]glycerol, remained in nerve. The oleate label was present as fatty acyl moieties in phospholipids and was localized to newly formed myelin sheaths. Among the extracellular soluble lipids within the degenerating nerve, the bulk of the labeled phospholipids floated at the same density as lipoprotein particles. These data indicate that myelin phospholipids are completely hydrolyzed during nerve degeneration, that at least half the resultant free fatty acids are salvaged and reutilized for new myelin synthesis, and that these salvaged fatty acids are transported by a lipoprotein‐mediated mechanism similar to that functioning in cholesterol reutilization.