Sphingolipids and Phospholipids of Myelin in Multiple Sclerosis

Cumings, J. N.; Goodwin, H.

doi:10.1016/s0140-6736(68)92510-5

Cited by 53 publications

(25 citation statements)

References 5 publications

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“…In these previous studies, serine and ino sitol phosphatides were not separated and concentrations were given for the sum of both glycerophosphatides. In this study we were able to sepa rate these two phospholipid classes by two-dimensional thin-layer chro matography and to show that the molar ratio of SPG:IPG is approximately 3:1 for normal human myelin ( [6] and Cumings and Goodwin [5] for the myelin of three cases of MS, and those of G erstl et al [11] for two other cases. These investigators ob tained less cerebroside for MS than for normal myelin, with a concomi tant increase of sulfatide.…”

Section: Discussionmentioning

confidence: 81%

“…Several investigators have found depletion of lipids and changes in the fatty acid pattern of individual lipid classes in areas of apparently normal white matter in multiple sclerosis (MS) and other demyelinating diseases [1,5,10,22). These observations suggest that patients with MS might have abnormalities of brain lipid metabolism (for instance an inadequacy Abbreviations: Fatty acids are denoted by chain length: number of double bonds; n-6 denotes the first double bond six carbons from the methyl group of the fatty acid chain.…”

Section: Myelin Multiple Sclerosis Phosphoglycerides Galactolipids Famentioning

confidence: 99%

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Lipid and Fatty Acid Composition of Myelin Purified from Normal and MS Brains

Woelk¹,

Borri²

1973

Eur Neurol

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The concentrations of phospholipids and galactolipids and their fatty acid compositions were determined in purified myelin from apparently normal white matter of 11 multiple sclerosis (MS) and 11 control brains. Myelin from MS brains showed a significant decrease in serine phosphatide and a slight decrease in the ethanolamine phosphatide fraction when compared with normal myelin; increases were found in the lysocholine and lysoethanolamine phosphoglycerides. In the galactolipids, lower figures were obtained for sulfatides, resulting in a higher cerebroside/sulfatide ratio for MS myelin. Analysis of the fatty acid pattern of phospholipids in MS brains revealed lower values for 18:1 and, except for the lyso compounds, slightly higher amounts for 20:4 and 22:6. Lower levels for the sum of 18:3 and 20:1 fatty acids were found for the EPG and IPG fractions.

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Section: Discussionmentioning

confidence: 81%

Section: Myelin Multiple Sclerosis Phosphoglycerides Galactolipids Famentioning

confidence: 99%

Lipid and Fatty Acid Composition of Myelin Purified from Normal and MS Brains

Woelk¹,

Borri²

1973

Eur Neurol

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“…Earlier studies of MS myelin lipid composition have reported variable results (Cumings, 1953;Gerstl et al, 1961;Davidson and Wajda, 1962; Cum- ings and Goodwin, 1968;Clausen and Hansen, 1970;Gerstl et al, 1970;Alling et al, 1971;Rinne et al, 1972;Gopfert et al, 1980;Husted et al, 1994). This is due not only to technological limitations in the analysis of the complicated lipid mixture from myelin, but also to the random occurrence of myelin changes throughout the brain and spinal cord with regard to both position and time in MS.…”

Section: Discussionmentioning

confidence: 99%

Atomic Force Microscopy of Nonhydroxy Galactocerebroside Nanotubes and Their Self-Assembly at the Air–Water Interface, with Applications to Myelin

Ohler

Revenko

Husted

2001

Journal of Structural Biology

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Myelin is one of the few biological membranes to contain the lipid galactocerebrosides, although their role in myelin is unclear. To explore its structural role, we used fluorescence and atomic force microscopy (AFM) to study nonhydroxy galactocerebrosides (NCer) at the air-water interface of a Langmuir-Blodgett trough. Fluorescence microscopy at the air-water interface indicated that NCer forms micrometer scale domains of varying radii with six fractal-like extensions. Atomic force microscopy using TappingMode in water on samples transferred to mica confirmed the fractal-like domain structure in the absence of dye and showed that the domains consisted of many aggregated nanotubes with a diameter of 30 nm. The Hausdorf fractal dimension was estimated to be 1.26 and 1.11 for two domains imaged with AFM. This evidence indicates that NCer forms a bulk phase of nanotubes at the air-water interface, unlike the liquidcondensed phase of a phospholipid monolayer. That NCer forms bilayer nanotubes that aggregate strongly suggests NCer helps maintain the stability of myelin by contributing to the curvature and adhesion of the membrane. We found that NCer appears to be decreased in myelin from multiple sclerosis normal appearing white matter, which could be an important event in the loss of myelin stability.

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“…This finding does not, however, rule out the possibility that the normal metabolism of myelin sheath is disturbed before any lysosomal changes are seen by electron microscopy [3,19,34], That this may be the case is suggested by chemical studies, which show that the different compo nents of myelin are affected at different stages of the disease [10,15,16,30], If myelin were degraded solely by the peeling-off process and subsequent 'bulk' digestion in the lysosomes, one would expect that dif ferent constituents would be lost approximately in the same proportion as they are present normal myelin. One possibility which must be taken into account in the degradation of myelin is the fact that purified myelin fractions both from CNS and from PNC contain proteinase activity as an integral of the membrane [1,18,21].…”

Section: Lysosomal Alterations and Their Relationship To Demyelinationmentioning

confidence: 93%

Studies on the Pathogenesis of Multiple Sclerosis

Riekkinen

et al. 1973

Eur Neurol

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The role of lysosomes in the pathogenesis of MS was studied by biochemical and ultrastructural techniques. Biochemical studies were performed on samples from 21 MS autopsies. The analyses included assays of acid proteinase, acid phosphatase, peptidase, neutral proteinase and esterase. The material for electron microscopy was obtained from ten biopsies made on MS patients during stereotaxic thalamotomy. In preliminary studies, the effect of autolysis on enzymatic activities was measured. These studies showed that acid hydrolases were stable enough to warrant further investigation. All enzyme activities studied were increased at the border zones of plaques, whereas in the macroscopically normal white matter only acid hydrolase activities were increased. Correspondingly, in electron microscopic studies, increased lysosomal response was found especially in astrocytes but also in oligodendrocytes. In astrocytes the number of heterolysosomes was conspicously increased and they were seen both in the perikaryon and in the cell processes. Such lysosomes often contained myelin-like membrane material. The presence of foreign phagocytizing cells could not be demonstrated except around the blood vessels. Furthermore, it appeared that myelin layers were not phagocytized by direct peeling process. These studies, suggest that early lysosomal changes occur in MS white matter and that such changes are mainly due to the phagocytosis of myelin inside astrocyte lysosomes. The possibility that the astrocyte response is a secondary phenomenon, which is preceded by other myelin destroying mechanisms is discussed.

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Sphingolipids and Phospholipids of Myelin in Multiple Sclerosis

Cited by 53 publications

References 5 publications

Lipid and Fatty Acid Composition of Myelin Purified from Normal and MS Brains

Lipid and Fatty Acid Composition of Myelin Purified from Normal and MS Brains

Atomic Force Microscopy of Nonhydroxy Galactocerebroside Nanotubes and Their Self-Assembly at the Air–Water Interface, with Applications to Myelin

Studies on the Pathogenesis of Multiple Sclerosis

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