Is the myelin membrane abnormal in multiple sclerosis?

Wood, D. D.; Moscarello, Mario A.

doi:10.1007/bf01871058

Cited by 38 publications

(21 citation statements)

References 82 publications

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“…This technique may improve the sensitivity and specificity of diagnosis and therapeutic monitoring of diseases that specifically target myelin. For instance, in multiple sclerosis plaques, biochemical studies have shown that there is a decrease in total lipid as well as myelin basic protein as a result of myelin loss (33). Many drugs have been designed to enhance re-myelination (34), however, the lack of a robust biomarker for re-myelination has remained problematic.…”

Section: Discussionmentioning

confidence: 99%

Direct magnitude and phase imaging of myelin using ultrashort echo time (UTE) pulse sequences: A feasibility study

Fan

et al. 2017

Magnetic Resonance Imaging

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In this paper, we aimed to investigate the feasibility of direct visualization of myelin, including myelin lipid and myelin basic protein (MBP), using two-dimensional ultrashort echo time (2D UTE) sequences and utilize phase information as a contrast mechanism in phantoms and in volunteers. The standard UTE sequence was used to detect both myelin and long T2 signal. An adiabatic inversion recovery UTE (IR-UTE) sequence was used to selectively detect myelin by suppressing signal from long T2 water protons. Magnitude and phase imagingand T2* were investigated on myelin lipid and MBP in the forms of lyophilized powders as well as paste-like phantoms with the powder mixed with D2O, and rubber phantoms as well as healthy volunteers. Contrast to noise ratio (CNR) between white and gray matter was measured. Both magnitude and phase images were generated for myelin and rubber phantoms as well white matter in vivo using the IR-UTE sequence. T2* values of ∼300 μs were comparable for myelin paste phantoms and the short T2* component in white matter of the brain in vivo. Mean CNR between white and gray matter in IR-UTE imaging was increased from -7.3 for the magnitude images to 57.4 for the phase images. The preliminary results suggest that the IR-UTEsequence allows simultaneous magnitude and phase imaging of myelin in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Direct magnitude and phase imaging of myelin using ultrashort echo time (UTE) pulse sequences: A feasibility study

Fan

et al. 2017

Magnetic Resonance Imaging

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“…* -P values multiplied by 5 to correct for multiple comparisons [3][4][5][6][7][8][9][10][11][12] spectra from each subject are indicated by circles for controls and squares for MS patients. The 19 symbols centered above the group labels reflect mean values obtained for each subject.…”

Section: Discussionmentioning

confidence: 99%

1H MRSI of normal appearing white matter in multiple sclerosis

et al. 1997

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The primary goal of this study was to determine if differences in proton magnetic resonance spectroscopy signals exist between normal appearing white matter (NAWM) of multiple sclerosis (MS) patients and white matter of control subjects. Water suppressed proton magnetic resonance spectroscopic imaging was used to determine the signal intensities of N-acetylated moieties (NA, predominantly N-acetylaspartate (NAA) the putative neuronal marker), creatine and phosphocreatine (Cr), and cholines (Ch) in 19 MS patients (15 relapsing-remitting and four secondary progressive) and 19 age matched control subjects. NA/Cr was significantly reduced (P < 0.001) in MS NAWM (1.8 +/- 0.2; x +/- s.d.) distant from MRI detected lesion areas compared to white matter of control subjects (2.1 +/- 0.2). This reduction was due to an increase in Cr from 0.39 +/- 0.04 (arbitrary units) in controls to 0.45 +/- 0.05 in MS patients. There was no significant change in NA or Ch in MS NAWM compared to controls. NA/Cr, distant from MRI lesion, was negatively correlated with total brain lesion volume as measured from T2-weighted MRI. We interpret the reduced NA/Cr in MS NAWM to indicate diffuse microscopic disease.

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“…The bilayers used in our experiments were modeled on the complex distribution of the lipids and proteins in native myelin membranes (12), although the choice of representative lipids was complicated by conflicting reports of the lipid compositions of healthy and diseased myelin and brain white matter in multiple sclerosis (3,(12)(13)(14)(15). Our choices for the compositions of the ''healthy'' and ''diseased'' lipid bilayers (Table 1) were based on a previous study (12) in which we simplified the differences by simply enriching the phosphatidylcholine (PC) mole fraction of the diseased lipid mixture by 50% while keeping the relative amounts of the other lipids the same.…”

Section: Methodsmentioning

confidence: 99%

“…Myelin acts as a transmitter of electric signals known as action potentials, its efficiency being attributed to the low dielectric constant associated with the high lipid content of its closely apposed membranes. Electrical impulses are transmitted along myelinated axons orders of magnitude faster than along unmyelinated axons (2)(3)(4). There are a number of human diseases, of which multiple sclerosis is the most common, that result in damage to the myelin sheath through membrane de-adhesion and swelling (demyelination or vacuolization) and ultimate vesiculation (5,6).…”

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confidence: 99%

Synergistic interactions of lipids and myelin basic protein

Doudevski

Wood

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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This report describes force measurements and atomic force microscope imaging of lipid-protein interactions that determine the structure of a model membrane system that closely mimics the myelin sheath. Our results suggest that noncovalent, mainly electrostatic and hydrophobic, interactions are responsible for the multilamellar structure and stability of myelin. We find that myelin basic protein acts as a lipid coupler between two apposed bilayers and as a lipid ''hole-filler,'' effectively preventing defect holes from developing. From our protein-mediated-adhesion and forcedistance measurements, we develop a simple quantitative model that gives a reasonably accurate picture of the molecular mechanism and adhesion of bilayer-bridging proteins by means of noncovalent interactions. The results and model indicate that optimum myelin adhesion and stability depend on the difference between, rather than the product of, the opposite charges on the lipid bilayers and myelin basic protein, as well as on the repulsive forces associated with membrane fluidity, and that small changes in any of these parameters away from the synergistically optimum values can lead to large changes in the adhesion or even its total elimination. Our results also show that the often-asked question of which membrane species, the lipids or the proteins, are the ''important ones'' may be misplaced. Both components work synergistically to provide the adhesion and overall structure. A better appreciation of the mechanism of this synergy may allow for a better understanding of stacked and especially myelin membrane structures and may lead to better treatments for demyelinating diseases such as multiple sclerosis.lipid-protein interactions ͉ myelin membrane structure ͉ membrane adhesion ͉ membrane regeneration͞healing ͉ demyelinating diseases T his communication addresses the general question of the molecular interactions that determine the structure and stability of membranes that are stabilized by bridging proteins, with the myelin sheath of the central nervous system (CNS) being taken as a prime example of this type of structure. The myelin sheath is formed by extensions of oligodendrocyte cell membranes that wrap around the axon to form a cylindrical scroll a few tens of micrometers in diameter (1, 2). The sheath consists of repeat units of ''double'' bilayers separated by 3-to 4-nm-thick aqueous layers that alternate between the cytoplasmic and extracellular spaces (2). Seventy to 80% of the dry weight of myelin consists of lipids, a proportion that is significantly higher than in most other cell membranes. There are two major proteins: myelin basic protein (MBP), which spans the aqueous cytoplasmic spaces, and proteolipid protein, which spans the bilayers (2). Myelin acts as a transmitter of electric signals known as action potentials, its efficiency being attributed to the low dielectric constant associated with the high lipid content of its closely apposed membranes. Electrical impulses are transmitted along myelinated axons orders of magnitude...

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Is the myelin membrane abnormal in multiple sclerosis?

Cited by 38 publications

References 82 publications

Direct magnitude and phase imaging of myelin using ultrashort echo time (UTE) pulse sequences: A feasibility study

Direct magnitude and phase imaging of myelin using ultrashort echo time (UTE) pulse sequences: A feasibility study

1H MRSI of normal appearing white matter in multiple sclerosis

Synergistic interactions of lipids and myelin basic protein

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