Myelin structure transformed by dimethylsulfoxide.

Abstract

X-ray diffraction patterns from nerves bathed for about one-half hour in Ringer's solution containing dimethylsulfoxide at concentrations of 10% or more show reflections from a new, highly ordered structure with a repeat period about two-thirds that of native myelin. The proportion of myelin transformed is greater at higher concentrations, and above 40% the native pattern is no longer observed. Replacing the dimethylsulfoxide with Ringer's solution leads to the rapid reappearance of the native diffraction pattern. The effect of dimethylsulfoxide can be accounted for by the loss of water from the spaces between the membrane units without significant modification of the bilayer structure.The molecular interactions that stabilize the spirally wrapped membrane array in the myelin sheath can be characterized by defining conditions that produce reversible structural modifications. Among the reagents we have tested for their effect on myelin structure, dimethylsulfoxide (Me2SO) is distinctive in producing an ordered transformation that is fully reversible.At concentrations above 40%, where the x-ray diffraction patterns show complete transformation of the myelin structure, Me2SO has been shown to produce reversible blockage of nerve conduction in vivo (1) and in isolated nerves (2); at lower concentrations, Me2SO decreases the conduction velocity (3). These physiological effects could be due to the action of Me2SO on both myelin sheath insulation and axon membrane excitability. Whatever the mechanism of these effects, removal of Me2SO restores normal nerve conduction (1-3), and our studies show that the myelin sheath also recovers its normal structure. Native myelins in a variety of nerves have repeat periods in the range 150-185 A (4, 5). The repeating unit is the membrane pair derived by joining cytoplasmic surfaces of the extension from a Schwann or glial cell plasma membrane (6, 7). Electron density profiles show that the membrane bilayers of different myelins have quite similar thickness although the repeat periods may be quite different (8). The spaces between bilayer surfaces comprise about onequarter of the repeat period in rabbit optic nerve and more than one-third the period in rabbit and frog sciatic nerves. Measurement of absolute electron density (9) indicates that these spaces are occupied by a low concentration of protein in water (8). The total water content in the myelin sheath has been estimated to be in the range 30-50% (4,8,10,11 during the appearance of the contracted lattice. This structure formed in Me2SO appears to be a distinct phase derived from native myelin.The exact period of the contracted phase is a function of Me2SO concentration and time of treatment. When first detected, the period is 7-9 A greater than the final value when the contraction has come to equilibrium (Fig. 1). The decrease in period with time roughly parallels the increase in diffracted intensity from the contracted phase. The strong second-order reflection (Fig. 2, top) accounts for about 95% of the total intensit...

Triethyl tin-induced myelin oedema: an intermediate swelling state detected by X-ray diffraction

“…The lower concentration is at least 50 times less than the threshold concentrations of other reagents that modify membrane packing in myelin, e.g. 5-10 mM Ca +2 or tetracaine (Melchior et al, 1979), 1.4 M dimethylsulphoxide (Kirschner & Caspar, 1975), and 250/~M HgC12 (Kirschner & Ganser, 1982). The 4/~M TET level is similar to that found in brains of developing rats chronically dosed with drinking water containing 10 mg TET/litre (Blaker et al, 1981).…”

“…Integrated intensities of the reflections were measured by numerical integration of the area under the peaks after background subtraction. The relative amount of myelin in the swollen and native phases, which is proportional to the relative diffracting power of that membrane array, was calculated from the intensity of the reflections belonging to that phase (for details, see Kirschner & Caspar, 1975).…”

An X-ray diffraction study of changes in myelin structure during experimental allergic neuritis

“…Formally, it is possible to measure the amount of myelin present in each sciatic nerve by calculating the peak value at the origin of the Patterson function (Kirschner & Caspar, 1975). Thick sections of sciatic nerves stained with reduced silver nitrate from a normal rat (c) and an EAN rat (d).…”

Plasmalogen phospholipids protect internodal myelin from oxidative damage

“…The Cu/OP/ HP-induced effect is presumably mediated by hydroxyl radicals [1,56,57], as evidenced by the protective effect of the hydroxyl radical scavenger sodium formate. Compared to the irreversible, Cu/OP/HPinduced compaction found here, the compaction of myelin to similar periods ($ 120 Å) with DMSO treatment is reversed by subsequent incubation in PBS [58]. The latter effect is attributed to the loss of water from the spaces between the myelin membranes, and to the lateral mobility of the transmembrane and extrinsic proteins in the myelin membranes [59].…”

“…Such data are quantified not only by measuring the period, but also by dividing the scatter from the myelin arrays by the total scatter from the nerve. This metric has been used previously to quantitate the percentage of myelin that is packed in its native form [39,44,58]. Here, quantification of the patterns (Fig.…”