Home About us Contact
|
Home About us Contact | ||
|
|
||
Myelin Formation (myelin + formation)
Selected AbstractsAbnormal myelin formation in rhizomelic chondrodysplasia punctata type 2 (DHAPAT-deficiency)DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 7 2000László Sztriha MD PhD The case of a Yemeni girl with isolated peroxisomal acyl-CoA:dihydroxyacetonephosphateacyltransferase (DHAPAT) deficiency is reported. She had rhizomelic chondrodysplasia punctata, microcephaly, failure to thrive, delayed motor and mental development, and spastic quadriplegia. Deficient de novo plasmalogen synthesis in her fibroblasts as a result of low DHAPAT activity was found, while her very-long-chain fatty acid profile, phytanic acid concentration, alkyl-dihydroxyacetonephosphate synthase (alkyl-DHAP synthase) activity, and peroxisomal 3-ketoacyl-CoA thiolase protein were normal. A mutation in her DHAPAT complementary DNA resulted in the substitution of an arginine residue in the protein at position 211 by a histidine (R211H). Magnetic resonance imaging showed abnormal white matter signal in the centrum semiovale involving the arcuate fibers, while the corpus callosum was normal. DHAPAT and alkyl-DHAP synthase initiate the synthesis of plasmalogens, which are major constituents of myelin phospholipids. The reported girl's abnormal formation of myelin is probably related to the inadequacy of plasmalogen biosynthesis, which is likely to be due to deficient DHAPAT activity. [source] Effects of early weaning on anxiety and prefrontal cortical and hippocampal myelination in male and female wistar ratsDEVELOPMENTAL PSYCHOBIOLOGY, Issue 4 2008Yuka Kodama Abstract We investigated developmental changes in myelin formation in the prefrontal cortex and the hippocampus, and behavioral effects of early weaning in Wistar rats. Early-weaned rats showed decreased numbers of open-arm entries in an elevated plus-maze in both sexes at 4 weeks old; this effect persisted in males, but ceased in females after this age. Expression of myelin basic protein (MBP) showed both age-dependent increases and sex differences; 4-week-old males exhibited higher MBP levels in the hippocampus, whereas 7-week-old males showed lower MBP levels in the prefrontal cortex compared to females of the same age. There was a tendency for group differences from weaning for the 21.5-kDa isoform in the prefrontal cortex. Although these results suggest that male rats are more vulnerable than females to early-weaning effects on anxiety-related behaviors, further detailed analysis is needed to clarify the functional relationship between myelination and anxiety-related behaviors. © 2008 Wiley Periodicals, Inc. Dev Psychobiol 50: 332,342, 2008. [source] Delay of myelin formation in arylsulphatase A-deficient miceEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2005Afshin Yaghootfam Abstract Metachromatic leukodystrophy (MLD) is a lysosomal storage disorder caused by the deficiency of arylsulphatase A (ASA). This leads to the accumulation of the sphingolipid 3-O-sulphogalactosylceramide (sulphatide) and progressive demyelination in the nervous system of MLD patients. The mechanisms and development of pathology in the disease are still largely unknown. In this study we investigate how the inability to degrade sulphatide affects the formation of myelin in ASA-deficient (ASA,/,) mice. In mice at 2 weeks of age there was a substantial reduction in myelin basic protein (MBP) mRNA and protein. This was confirmed by an immunohistochemical analysis. MBP mRNA and protein, however, reach normal levels at 3 weeks of age. Proteolipid protein (PLP) and MAL mRNA were also reduced in ASA,/, mice at 2 weeks of age; whereas the level of PLP mRNA was normal at 26 weeks of age, MAL mRNA expression remained reduced up to this age. In situ hybridization revealed no significant changes in the number of myelinating oligodendrocytes or oligodendrocyte precursor cells in ASA,/, mice. These results suggest that oligodendrocyte differentiation was normal in ASA,/, mice. No differences were found in the expression of the sulphatide synthesizing enzymes cerebroside sulphotransferase and UDP-galactose : ceramide galactosyltransferase. Our data demonstrate a delay in myelin formation in ASA,/, mice. This raises the possibility that similar alterations in MLD patients may contribute to the pathology of the disease. [source] Matrix metalloproteinase-2 is involved in myelination of dorsal root ganglia neuronsGLIA, Issue 5 2009Helmar C. Lehmann Abstract Matrix metalloproteinases (MMPs) comprise a large family of endopeptidases that are capable of degrading all extracellular matrix components. There is increasing evidence that MMPs are not only involved in tissue destruction but may also exert beneficial effects during axonal regeneration and nerve remyelination. Here, we provide evidence that MMP-2 (gelatinase A) is associated with the physiological process of myelination in the peripheral nervous system (PNS). In a myelinating co-culture model of Schwann cells and dorsal root ganglia neurons, MMP-2 expression correlated with the degree of myelination as determined by immunocytochemistry, zymography, and immunosorbent assay. Modulation of MMP-2 activity by chemical inhibitors led to incomplete and aberrant myelin formation. In vivo MMP-2 expression was detected in the cerebrospinal fluid (CSF) of patients with Guillain-Barré syndrome as well as in CSF and sural nerve biopsies of patients with chronic inflammatory demyelinating polyneuropathy. Our findings suggest an important, previously unrecognized role for MMP-2 during myelination in the PNS. Endogenous or exogenous modulation of MMP-2 activity may be a relevant target to enhance regeneration in demyelinating diseases of the PNS. © 2008 Wiley-Liss, Inc. [source] Schwann cells and the pathogenesis of inherited motor and sensory neuropathies (Charcot-Marie-Tooth disease)GLIA, Issue 4 2006Philipp Berger Abstract Over the last 15 years, a number of mutations in a variety of genes have been identified that lead to inherited motor and sensory neuropathies (HMSN), also called Charcot-Marie-Tooth disease (CMT). In this review we will focus on the molecular and cellular mechanisms that cause the Schwann cell pathologies observed in dysmyelinating and demyelinating forms of CMT. In most instances, the underlying gene defects alter primarily myelinating Schwann cells followed by secondary axonal degeneration. The first set of proteins affected by disease-causing mutations includes the myelin components PMP22, P0/MPZ, Cx32/GJB1, and periaxin. A second group contains the regulators of myelin gene transcription EGR2/Krox20 and SOX10. A third group is composed of intracellular Schwann cells proteins that are likely to be involved in the synthesis, transport and degradation of myelin components. These include the myotubularin-related lipid phosphatase MTMR2 and its regulatory binding partner MTMR13/SBF2, SIMPLE, and potentially also dynamin 2. Mutations affecting the mitochondrial fission factor GDAP1 may indicate an important contribution of mitochondria in myelination or myelin maintenance, whereas the functions of other identified genes, including NDRG1, KIAA1985, and the tyrosyl-tRNA synthase YARS, are not yet clear. Mutations in GDAP1, YARS, and the pleckstrin homology domain of dynamin 2 lead to an intermediate form of CMT that is characterized by moderately reduced nerve conduction velocity consistent with minor myelin deficits. Whether these phenotypes originate in Schwann cells or in neurons, or whether both cell types are directly affected, remains a challenging question. However, based on the advances in systematic gene identification in CMT and the analyses of the function and dysfunction of the affected proteins, crucially interconnected pathways in Schwann cells in health and disease have started to emerge. These networks include the control of myelin formation and stability, membrane trafficking, intracellular protein sorting and quality control, and may extend to mitochondrial dynamics and basic protein biosynthesis. © 2006 Wiley-Liss, Inc. [source] Fibroblast growth factor receptor-3 null mice exhibit a delay in the development of oligodendrocytes and myelinationJOURNAL OF NEUROCHEMISTRY, Issue 2002R. Bansal Fibroblast growth factors (FGFs) comprise of a family of twenty-three members which bind to four receptor tyrosine kinases (R1,R4). They induce a broad spectrum of biological effects in a variety of cell types, including neurons and glia in the CNS. In oligodendrocytes (OLs), FGF-2 elicits a number of specific responses depending on their stage of development. During OL development in vitro, the expressions of FGF-receptor mRNAs are differentially regulated. R1 mRNA increases gradually along with OL maturation, whereas R3 and R2 mRNAs peak at the OL progenitor and mature OL stages, respectively, suggesting a differential roles of these receptors in OL development. R3 is also expressed by astrocytes. To determine the roles of R3 during OL development and myelination in vivo, we have employed mice lacking functional R3 (R3-null). During myelination (P7, P9, P13), reduced numbers of differentiated OLs and myelinated fibers are observed in the brains of R3 null mice compared to wild type mice. Moreover, up-regulation of glial fibrillary acidic protein-positive astrocytes is found in the cerebellum and spinal cord of R3 null mutants. However, the number of OL progenitors (PDGF-Ra), BrdU incorporation, and cell survival (TUNEL assay) are all comparable, and R3-null myelin in adult mice appears to be similar to that of wild type mice. In mixed primary cultures of post-natal R3 null brain (that have few if any neurons), OLs exhibit a delay in differentiation similar to that observed in vivo. In summary, our results elucidate regulatory roles of FGF-R3 in mouse brain, in particular with regard to its roles in the timing of OL maturation and myelin formation (MS Society, Canada, NIH NS38878-03). [source] Crow,Fukase (POEMS) syndrome: a study of peripheral nerve biopsy in five new casesJOURNAL OF THE PERIPHERAL NERVOUS SYSTEM, Issue 3 2003Claude Vital Abstract, The pathogenesis of Crow,Fukase (POEMS) syndrome is not well known, and in some cases, a definite diagnosis is difficult to establish. Nerve fibers have been studied in about 120 peripheral nerve biopsies (PNBs), and a mixture of axonal and demyelinating lesions were found in most of them. We report five new cases of Crow,Fukase (POEMS) syndrome with ultrastructural examination of their PNBs. In every case, there were features of axonal degeneration and primary demyelination. Interestingly, uncompacted myelin lamellae (UMLs) were present in every case at a percentage of 1,7. The association of UML and Crow,Fukase (POEMS) syndrome was described 20 years ago but was only reported in a few studies and found in 31 of 41 cases. In fact, this association is very significant because apart from Crow,Fukase (POEMS) syndrome, UMLs can only be found with such a frequency in rare cases of Charcot,Marie,Tooth disease type 1B. UML was also reported in acute and chronic inflammatory demyelinating polyneuropathies but at a much lower percentage. Moreover, in our five cases, UML was frequently associated with a decrease in the number of intra-axonal filaments, and this finding raises the problem of relationships between myelin formation and neurofilaments. So far, glomeruloid hemangiomas present in the dermis of some patients are considered as the only specific criteria of Crow,Fukase (POEMS) syndrome, but we think UML can also be regarded as highly suggestive of this entity on condition that a thorough ultrastructural examination of a PNB is performed. [source] Tetraspanins and Intercellular InteractionsMICROCIRCULATION, Issue 3 2001MARÍA YÁŃEZ-MÓ ABSTRACT The superfamily of tetraspanins comprises a group of polypeptides with four transmembrane domains that form large supramolecular structures in the plasma membrane through their associations to multiple integral membrane proteins. They are involved in homo- and heterotypic intercellular interactions in different processes such as hematopoiesis, lymphocyte activation, cancer metastasis, and fertilization. Intercellularly located tetraspanins regulate the juxtacrine activity of growth factors, cell fusion, and myelin formation. On the other hand, in motile cells they relocalize from cell-cell junctions to actin-based structures such as filopodia or growth cones and regulate cell motility in wound healing and angiogenesis processes. [source] Sequential myelin protein expression during remyelination reveals fast and efficient repair after central nervous system demyelinationNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 1 2008M. Lindner To understand the mechanisms of remyelination and the reasons for regeneration failure is one of the major challenges in multiple sclerosis research. This requires a good knowledge and reliable analysis of experimental models. This work was undertaken to characterize the pattern of myelin protein expression during experimental remyelination. Acute demyelination of the corpus callosum was induced by feeding of 0.3% cuprizone for 6 weeks, followed by a 10-week remyelination period. We used a combination of Luxol fast blue (LFB) myelin staining, electron microscopy (EM) and immunohistochemistry for the myelin proteins 2,,3,-cyclic nucleotide 3, phosphodiesterase (CNPase), myelin basic protein (MBP), proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG). Early remyelination was detected by the re-expression of CNPase, MBP and PLP as early as 4 days. MOG, as a marker for late differentiation of oligodendrocytes, was not detectable until 2 weeks of remyelination. EM data correlated well with the LFB myelin staining and myelin protein expression, with 50% of the axons being rapidly remyelinated within 2 weeks. While particularly MBP but also PLP and CNPase are re-expressed very early before significant remyelination is observed by EM, the late marker MOG shows a lag behind the remyelination detected by EM. The presented data indicate that immunohistochemistry for various myelin proteins expressed early and late during myelin formation is a suitable and reliable method to follow remyelination in the cuprizone model. Furthermore, investigation of early remyelination confirms that the intrinsic repair programme is very fast and switched on within days. [source] Insulin-like growth factor-1 and neurotrophin-3 gene therapy prevents motor decline in an X-linked adrenoleukodystrophy mouse model,ANNALS OF NEUROLOGY, Issue 1 2009Roberto Mastroeni MSc X-linked adrenoleukodystrophy (X-ALD) is the most common inherited peroxisomal disorder characterized by a progressive demyelination of the central nervous system. The marked loss of myelin and oligodendrocytes observed in the disease prompted us to evaluate the therapeutic potential of insulin-like growth factor-1 and neurotrophin-3, two potent inducers of myelin formation and oligodendrocyte survival. Viral vectors engineered to produce insulin-like growth factor-1 or neurotrophin-3 were administrated into the cerebrospinal fluid of an X-linked adrenoleukodystrophy mouse model. We show that viral-based, long-lasting delivery of insulin-like growth factor-1 and neurotrophin-3 significantly halts the progression of the disease and leads to potent protective effect against the demyelination process. Ann Neurol 2009;66:117,122 [source] Oligodendrogenesis: The role of ironBIOFACTORS, Issue 2 2010Maria Elvira Badaracco Abstract Iron seems to be an essential factor in myelination and oligodendrocyte (OLGc) biology. However, the specific role of iron in these processes remains to be elucidated. Iron deficiency (ID) imposed to developing rats has been a relevant model to understand the role of iron in oligodendrogenesis and myelination. During early development ID causes specific changes in myelin composition, including a lower relative content of cholesterol, proteolipid protein (PLP), and myelin basic protein 21 (MBP21). These changes could be a consequence of the adverse effects of ID on OLGc development and function. We subsenquently studied the possible corrective effect of a single intracranial injection (ICI) of apotransferrin (aTf) on myelin formation in ID rats OLGc migration and differentiation after an ICI of aTf was evaluated at 3 days of age. ID increased the number of proliferating and undifferentiated cells in the corpus callosum (CC), while a single aTf injection reverts these effects, increasing the number of mature cells and myelin formation. Overall, results of a series of studies supports the concept that iron may affect OLGc development at early stages of embryogenesis rather than during late development. Myelin composition is altered by a limited iron supply, changes that can be reverted by a single injection of aTf. [source] Plasmalogen levels in full-term neonatesACTA PAEDIATRICA, Issue 4 2009I Labadaridis Abstract Aim: Plasmalogens are phospholipids characterized by the presence of a vinyl ether bond at the sn-1 position of the glycerol backbone. They are particularly abundant in the nervous system, the heart and striated muscle. Peroxisomes are essential for their biosynthesis and red blood cell (RBC) plasmalogen levels are a reliable test in the investigation of patients suspect for a peroxisomal defect. The functions attributed to them include protection against oxidative stress, myelin formation and signal transduction. The aim of the present study was the investigation of RBC plasmalogen levels in neonates. Methods: A total of 25 healthy full-term, appropriate for gestational age neonates were studied. RBC plasmalogens were estimated using gas chromatography within the first five days of life. Fifteen healthy children 1,8-year olds served as controls. Results: Statistically significant lower plasmalogen levels were found in neonates compared to older children. Conclusion: Our results indicate that a different range of normal values for plasmalogen levels should be used in the investigation of peroxisomal diseases in neonates. The lower levels of plasmalogens in neonates found in our study could render them more vulnerable to oxidative stress. [source] | |||||||||||||