2′, 3′‐Cyclic Nucleotide 3′‐Phosphohydrolase and Lipids of Myelin from Multiple Sclerosis and Normal Brains

Abstract

A study of purified myelin samples from normal‐appearing white matter of 10 multiple sclerosis (MS) brains was undertaken and the results were compared with 10 age‐matched control brains. Statistical evaluations were carried out with Student's r‐test for differences. In pathological samples the yield of myelin came to only two‐thirds of the corresponding controls. Enzyme assays of the 2′, 3′‐cyclic 3′‐phosphohydrolase revealed an obviously significant reduction of specific activity to one‐half in MS myelins. In myelin the contents of protein, lipid classes as cholesterol, glycolipids and phospholipids did not differ significantly. No cholesterol esters or any lysophospholipid were detectable either in MS or in controls. Within the individual phospholipids the main components were in the same order, while a significant decrease of the acidic representatives and of sphingomyelin occurred. Analysis of the fatty acid pattern of phosphatidylcholine (PC), phosphatidylserine (PS) and phosphatidylethanolamine (PE), including the aldehydes from the last, revealed quite similar values with no significant differences, except C22: 4 fatty acid in the PE fraction and C20: 1 fatty acid in PS, which were reduced in MS myelin samples.

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

“…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.…”

Is the myelin membrane abnormal in multiple sclerosis?

“…The cholesterol content is similar in both, and no cholesterol esters have been detected [37,45]. The cholesterol content is similar in both, and no cholesterol esters have been detected [37,45].…”

“…When the enzyme activity of 2',3 '-cyclic nucleotide 3'-phosphohydrolase purified from MS myelin was compared to the normal enzyme activity, it was found to be decreased by one half [45]. No significance was attached to this finding by the investigators as they could not establish whether the total enzyme concentration was decreased or whether half of the enzyme had been inactivated in some way.…”

Differential display PCR reveals increased expression of 2′,3′‐cyclic nucleotide 3′‐phosphodiesterase by lithium

“…CNPase has been investigated in the pathophysiology of several disorders including multiple sclerosis. For instance, CNPase activity was reduced to 50% of control values in postmortem brain white matter samples obtained from subjects with multiple sclerosis [42]. The fact that CNPaseII is involved in cell differentiation and myelinogenesis raises the possibility that lithium treatment may lead to its therapeutic effects in BD by regulating one of these processes.…”