			Home About us Contact

Myelin Abnormalities (myelin + abnormality)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

RESEARCH ARTICLE: Myelin Abnormalities without Oligodendrocyte Loss in Periventricular Leukomalacia

BRAIN PATHOLOGY, Issue 2 2008
Saraid S. Billiards
Abstract The cellular basis of myelin deficits detected by neuroimaging in long-term survivors of periventricular leukomalacia (PVL) is poorly understood. We tested the hypothesis that oligodendrocyte lineage (OL) cell density is reduced in PVL, thereby contributing to subsequent myelin deficits. Using computer-based methods, we determined OL cell density in sections from 18 PVL and 18 age-adjusted control cases, immunostained with the OL-lineage marker Olig2. Myelination was assessed with myelin basic protein (MBP) immunostaining. We found no significant difference between PVL and control cases in Olig2 cell density in the periventricular or intragyral white matter. We did find, however, a significant increase in Olig2 cell density at the necrotic foci, compared with distant areas. Although no significant difference was found in the degree of MBP immunostaining, we observed qualitative abnormalities of MBP immunostaining in both the diffuse and necrotic components of PVL. Abnormal MBP immunostaining in PVL despite preserved Olig2 cell density may be secondary to arrested OL maturation, damage to OL processes, and/or impaired axonal-OL signaling. OL migration toward the "core" of injury may occur to replenish OL cell number. This study provides new insight into the cellular basis of the myelin deficits observed in survivors of PVL. [source]

Absence of oligodendroglial glucosylceramide synthesis does not result in CNS myelin abnormalities or alter the dysmyelinating phenotype of CGT-deficient mice

GLIA, Issue 4 2010
Laleh Saadat
Abstract To examine the function of glycosphingolipids (GSLs) in oligodendrocytes, the myelinating cells of the central nervous system (CNS), mice were generated that lack oligodendroglial expression of UDP-glucose ceramide glucosyltransferase (encoded by Ugcg). These mice (Ugcgflox/flox;Cnp/Cre) did not show any apparent clinical phenotype, their total brain and myelin extracts had normal GSL content, including ganglioside composition, and myelin abnormalities were not detected in their CNS. These data indicate that the elimination of gangliosides from oligodendrocytes is not detrimental to myelination. These mice were also used to asses the potential compensatory effect of hydroxyl fatty acid glucosylceramide (HFA-GlcCer) accumulation in UDP-galactose:ceramide galactosyltransferase (encoded by Cgt, also known as Ugt8a) deficient mice. At postnatal day 18, the phenotypic characteristics of the Ugcgflox/flox;Cnp/Cre;Cgt,/, mutants, including the degree of hypomyelination, were surprisingly similar to that of Cgt,/, mice, suggesting that the accumulation of HFA-GlcCer in Cgt,/, mice does not modify their phenotype. These studies demonstrate that abundant, structurally intact myelin can form in the absence of glycolipids, which normally represent over 20% of the dry weight of myelin. © 2009 Wiley-Liss, Inc. [source]

Developmental abnormalities in the nerves of peripheral myelin protein 22-deficient mice

JOURNAL OF NEUROSCIENCE RESEARCH, Issue 2 2007
Stephanie A. Amici
Abstract Peripheral myelin protein 22 (PMP22) is a tetraspan glycoprotein whose misexpression is associated with a family of hereditary peripheral neuropathies. In a recent report, we have characterized a novel PMP22-deficient mouse model in which the first two coding exons were replaced by the lacZ reporter. To investigate further the myelin abnormalities in the absence of PMP22, sciatic nerves and dorsal root ganglion (DRG) neuron explant cultures from PMP22-deficient mice were studied at various stages of myelination. Throughout the first 3 months of postnatal development, myelin protein and ,4 integrin levels are dramatically reduced, whereas p75 and ,1 integrin remain elevated. By immunostaining, the distributions of several glial proteins, including ,4 integrin, the voltage-gated potassium channel Kv1.1, and E-cadherin, are altered. Schwann cells from PMP22-deficient mice are able to produce limited amounts of myelin in DRG explant cultures, yet the internodal segments are dramatically fewer and shorter. The comparison of PMP22-deficient mice with other PMP22 mutant models reveals that the decrease in ,4 integrin is specific to an absence of PMP22. Furthermore, whereas lysosome-associated membrane protein 1 and ubiquitin are notably up-regulated in nerves of PMP22-deficient mice, heat shock protein 70 levels remain constant or decrease compared with wild-type or PMP22 mutant samples. Together these results support a role for PMP22 in the early events of peripheral nerve myelination. Additionally, although myelin abnormalities are a commonality among PMP22 neuropathic models, the underlying subcellular mechanisms are distinct and depend on the specific genetic abnormality. © 2006 Wiley-Liss, Inc. [source]

White matter abnormalities in bipolar disorder: a voxel-based diffusion tensor imaging study

BIPOLAR DISORDERS, Issue 4 2008
Stefania Bruno
Objectives:, In bipolar disorder (BD), dysregulation of mood may result from white matter abnormalities that disrupt fronto-subcortical circuits. In this study, we explore such abnormalities using diffusion tensor imaging (DTI), an imaging technique capable of detecting subtle changes not visible with conventional magnetic resonance imaging (MRI), and voxel-based analysis. Methods:, Thirty-six patients with BD, all but two receiving antidepressants or mood stabilizers, and 28 healthy controls matched for age and gender were studied. Diffusion-weighted echoplanar images (DW-EPI) were obtained using a 1.5T scanner. Voxel-based analysis was performed using SPM 2. Differences between the groups in mean diffusivity and fractional anisotropy (FA) were explored. Results:, In the patient group, mean diffusivity was increased in the right posterior frontal and bilateral prefrontal white matter, while FA was increased in the inferior, middle temporal and middle occipital regions. The areas of increased mean diffusivity overlapped with those previously found to be abnormal using volumetric MRI and magnetization transfer imaging (MTI) in the same group of patients. Conclusions:, White matter abnormalities, predominantly in the fronto-temporal regions, can be detected in patients with BD using DTI. The neuropathology of these abnormalities is uncertain, but neuronal and axonal loss, myelin abnormalities and alterations in axonal packing density are likely to be relevant. The neuroprotective effects of some antidepressants and mood stabilizers make it unlikely that medication effects could explain the abnormalities described here, although minor effects cannot be excluded. [source]

Histological and Ultrastructural Analysis of White Matter Damage after Naturally-occurring Spinal Cord Injury

BRAIN PATHOLOGY, Issue 2 2006
Peter M. Smith
Detailed analysis of the structural changes that follow human clinical spinal cord injury is limited by difficulties in achieving adequate tissue fixation. This study bypasses this obstacle by examining the spinal cord from paraplegic domestic animals, enabling us to document the ultrastructural changes at different times following injury. In all but one case, injury resulted from a combination of contusion and compression. There was infarction and hemorrhage, followed by gray matter destruction and the rapid development of a variety of white matter changes including axon swelling and myelin degeneration. Axons greater than 5 µm in diameter were more susceptible to degenerative changes, whereas smaller axons, particularly those in the subpial region, were relatively well preserved. Demyelinated axons were seen within 2 weeks after injury and, at later time points, both Schwann cell and oligodendrocyte remyelination was common. More subtle white matter abnormalities were identified by examining sagittal sections, including focal accumulation of organelles in the axoplasm and partial and paranodal myelin abnormalities. These observations serve to validate observations from experimental models of spinal contusion but also highlight the complexity of naturally occurring (ie, clinical) spinal injury. They also raise the possibility that focal abnormalities such as paranodal demyelination may contribute to early axonal dysfunction and possibly to progressive tissue damage. [source]