The Experts below are selected from a list of 1680 Experts worldwide ranked by ideXlab platform
Yue Feng - One of the best experts on this subject based on the ideXlab platform.
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Essential function, sophisticated regulation and pathological impact of the selective RNA-binding protein QKI in CNS myelin development.
Future neurology, 2008Co-Authors: Katrina M. Bockbrader, Yue FengAbstract:The selective RNA-binding protein QKI play a key role in advancing oligodendrocyte-dependent myelination, which is essential for the function and development of the CNS. The emerging evidence that QKI abnormalities are associated with schizophrenia and may underlie myelin impairment in this devastating disease has greatly increased interest in understanding the function of QKI. Despite the discovery of the biochemical basis for QKI–RNA interaction, a comprehensive model is currently missing regarding how QKI regulates its mRNA ligands to promote normal Myelinogenesis and how deficiency of the QKI pathway is involved in the pathogenesis of human diseases that affect CNS myelin. In this review, we will focus on the role of QKI in regulating distinct mRNA targets at critical developmental steps to promote oligodendrocyte differentiation and myelin formation. In addition, we will discuss molecular mechanisms that control QKI expression and activity during normal Myelinogenesis as well as the pathological impa...
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rescuing qkv dysmyelination by a single isoform of the selective rna binding protein qki
The Journal of Neuroscience, 2006Co-Authors: Lixia Zhao, Donghua Tian, Mingjing Xia, Wendy B Macklin, Yue FengAbstract:Alternative splicing of the qkI transcript generates multiple isoforms of the selective RNA-binding protein QKI, which play key roles in controlling the homeostasis of their mRNA targets. QKI deficiency in oligodendrocytes of homozygous quakingviable (qkv/qkv) mutant mice results in severe hypomyelination, indicating the essential function of QKI in Myelinogenesis. However, the molecular mechanisms by which QKI controls myelination remain elusive. We report here that QKI-6 is the most abundant isoform in brain and is preferentially reduced in the qkv/qkv mutant during normal Myelinogenesis. To test whether QKI-6 is the predominant isoform responsible for advancing CNS myelination, we developed transgenic mice that express Flag-QKI-6 specifically in the oligodendroglia lineage, driven by the proteolipid protein (PLP) promoter. When introduced into the qkv/qkv mutant, the QKI-6 transgene rescues the severe tremor and hypomyelination phenotype. Electron microscopic studies further revealed that the Flag-QKI-6 transgene is sufficient for restoring compact myelin formation with normal lamellar periodicity and thickness. Interestingly, Flag-QKI-6 preferentially associates with the mRNA encoding the myelin basic protein (MBP) and rescues MBP expression from the beginning of Myelinogenesis. In contrast, Flag-QKI-6 binds the PLP mRNA with lower efficiency and has a minimal impact on PLP expression until much later, when the expression level of QKI-6 in the transgenic animal significantly exceeds what is needed for normal myelination. Together, our results demonstrate that QKI-6 is the major isoform responsible for CNS myelination, which preferentially promotes MBP expression in oligodendrocytes.
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Developmental abnormalities of myelin basic protein expression in fyn knock-out brain reveal a role of Fyn in posttranscriptional regulation.
The Journal of biological chemistry, 2004Co-Authors: Yuntao Chen, Yue FengAbstract:Fyn protein-tyrosine kinase (PTK), a member of the Src-PTK family, is essential for myelin development in the central nervous system (CNS). The absence of Fyn activity results in defects in the morphogenesis of oligodendrocyte precursors (OPCs) and CNS hypomyelination. However, molecular mechanisms for Fyn to control CNS Myelinogenesis remain elusive. Here we show that Fyn-PTK is significantly up-regulated in early OPC differentiation, concentrated in the compact myelin, and declines during myelin development. Despite the high levels of Fyn-PTK expression during early OPC differentiation, Fyn deficiency does not affect the expression of mRNAs that encode myelin structural proteins, including that for the myelin basic protein (MBP), until postnatal day 13 (P13). However, the accumulation rate of MBP mRNA is significantly attenuated during the most active period of Myelinogenesis (P13 and P20). Interestingly, the absence of Fyn causes a preferential reduction of the exon-2 containing MBP mRNA isoforms derived from alternative splicing, providing the first evidence that Fyn is required for posttranscriptional regulation of MBP. Consistent with this idea, Fyn phosphorylates the selective RNA-binding protein QKI, which likely modulates the activity of QKI in binding and stabilizing the MBP mRNA. Furthermore, Fyn deficiency exerts an opposing influence on MBP isoform patterning in comparison to that by QKI deficiency. These observations collectively suggest that Fyn plays critical roles in promoting accelerated MBP expression during Myelinogenesis in a MBP isoform-preferential manner, and QKI may act in the same pathway downstream of Fyn for MBP mRNA homeostasis.
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Tyrosine phosphorylation of QKI mediates developmental signals to regulate mRNA metabolism
The EMBO journal, 2003Co-Authors: Youyi Zhang, Yuntao Chen, Houping Wang, Yue FengAbstract:The selective RNA-binding protein QKI is essential for myelination in the central nervous system (CNS). QKI belongs to the family of signal transduction activators of RNA (STARs), characteristic of binding RNA and signaling molecules, therefore is postulated to regulate RNA homeostasis in response to developmental signals. Here we report that QKI acts downstream of the Src family protein tyrosine kinases (Src-PTKs) during CNS myelination. QKI selectively interacted with the mRNA encoding the myelin basic protein (MBP). Such interaction stabilized MBP mRNA and was required for the rapid accumulation of MBP mRNA during active Myelinogenesis. We found that the interaction between QKI and MBP mRNA was negatively regulated by Src-PTK-dependent phosphorylation of QKI. During early myelin development, tyrosine phosphorylation of QKI in the developing myelin drastically declined, presumably leading to enhanced interactions between QKI and MBP mRNA, which was associated with the rapid accumulation of MBP mRNA and accelerated myelin production. Therefore, developmental regulation of Src-PTK-dependent tyrosine phosphorylation of QKI suggests a novel mechanism for accelerating CNS Myelinogenesis via regulating mRNA metabolism.
Serafina Salvati - One of the best experts on this subject based on the ideXlab platform.
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eicosapentaenoic acid in Myelinogenesis prospective in multiple sclerosis treatment
2017Co-Authors: A. Di Biase, Lucilla Attorri, R Di Benedetto, Serafina SalvatiAbstract:Abstract There is evidence that increased intake of fish oil, rich in long-chain n-3 polyunsaturated fatty acids, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may beneficially affect the development and course of multiple sclerosis. However, controlled trials have not been able to draw definitive conclusions. The conflicting results could be due to the different mixture of EPA and DHA present in different sources of fish oils used in the clinical trials. In fact, among n-3 polyunsaturated fatty acids, EPA has the most potent effect on Myelinogenesis and inflammatory process. The purpose of this chapter is to review the current knowledge on mechanisms underlying these beneficial effects and the evidence of neurological benefits of EPA, looking specifically at multiple sclerosis.
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Chapter 27 – Eicosapentaenoic Acid in Myelinogenesis: Prospective in Multiple Sclerosis Treatment
Nutrition and Lifestyle in Neurological Autoimmune Diseases, 2017Co-Authors: A. Di Biase, Lucilla Attorri, R Di Benedetto, Serafina SalvatiAbstract:There is evidence that increased intake of fish oil, rich in long-chain n-3 polyunsaturated fatty acids, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may beneficially affect the development and course of multiple sclerosis. However, controlled trials have not been able to draw definitive conclusions. The conflicting results could be due to the different mixture of EPA and DHA present in different sources of fish oils used in the clinical trials. In fact, among n-3 polyunsaturated fatty acids, EPA has the most potent effect on Myelinogenesis and inflammatory process. The purpose of this chapter is to review the current knowledge on mechanisms underlying these beneficial effects and the evidence of neurological benefits of EPA, looking specifically at multiple sclerosis.
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chapter 27 eicosapentaenoic acid in Myelinogenesis prospective in multiple sclerosis treatment
Nutrition and Lifestyle in Neurological Autoimmune Diseases#R##N#Multiple Sclerosis, 2017Co-Authors: A. Di Biase, Lucilla Attorri, R Di Benedetto, Serafina SalvatiAbstract:There is evidence that increased intake of fish oil, rich in long-chain n-3 polyunsaturated fatty acids, mainly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may beneficially affect the development and course of multiple sclerosis. However, controlled trials have not been able to draw definitive conclusions. The conflicting results could be due to the different mixture of EPA and DHA present in different sources of fish oils used in the clinical trials. In fact, among n-3 polyunsaturated fatty acids, EPA has the most potent effect on Myelinogenesis and inflammatory process. The purpose of this chapter is to review the current knowledge on mechanisms underlying these beneficial effects and the evidence of neurological benefits of EPA, looking specifically at multiple sclerosis.
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Accelerated Myelinogenesis by dietary lipids in rat brain.
Journal of neurochemistry, 2002Co-Authors: Serafina Salvati, Massimo Sanchez, L. Malvezzi Campeggi, Gerda Suchanek, Helene Breitschop, Hans LassmannAbstract:: Our previous work showed an early development of behavioral reflexes in rats whose mothers had been fed, during pregnancy and lactation, a lipid fraction extracted from yeast grown on n-alkanes (which contain 50% odd-chain fatty acids) in comparison with controls fed a margarine diet. To clarify whether the observed changes might be linked to an early myelination, we have investigated mRNAs involved in myelin synthesis in the brains of offspring at 5 days of age by northern blot and in situ hybridization. Northern blot analysis showed that proteolipid protein (PLP) and myelin oligodendrocyte glycoprotein (MOG) mRNAs were higher in animals on the lipid diet compared with controls. In situ hybridization with probes specific for PLP, myelin basic protein, and MOG mRNA showed significantly higher numbers of positive cells in test animals compared with controls in all brain regions. This study shows an acceleration of Myelinogenesis induced by dietary lipids. These data can give a new insight in the therapeutical approaches involved to promote repair in demyelinating diseases.
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Diet, lipids and brain development.
Developmental neuroscience, 2000Co-Authors: Serafina Salvati, Lucilla Attorri, C. Avellino, A. Di Biase, Massimo SanchezAbstract:Brain development is a sequential anatomical process characterised by specific well-defined stages of growth and maturation. One of the fundamental and necessary events in the normal development of the central nervous system in vertebrates is the formation of a myelin sheath. It is becoming more evident that this process is influenced by dietary lipids. A number of findings have indicated that the administration of a diet deficient in essential fatty acids during development causes hypomyelination in the rat brain. Our studies have shown that lipids can also play a role in accelerating Myelinogenesis in the brain of rats whose mothers had been fed, during pregnancy and lactation, a lipid fraction extracted from yeast grown on n-alkanes. Further studies have shown that accelerated Myelinogenesis is connected to a precocious appearance of behavioural reflexes. Thus, the use of particular lipids in human nutrition must be carefully screened for possible effects on brain development.
Leonard H. Rome - One of the best experts on this subject based on the ideXlab platform.
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Expression of a/31-Related Integrin by Oligodendroglia in Primary Culture: Evidence for a Functional Role in Myelination
2013Co-Authors: Shahnaz Malek-hedayat, Leonard H. RomeAbstract:Abstract. We have investigated the expression of integrins by rat oligodendroglia grown in primary culture and the functional role of these proteins in Myelinogenesis. Immunochemical analysis, using antibodies to a number of ot and/3 integrin subunits, revealed that oligodendrocytes express only one detectable integrin receptor complex (CtO~OL). This complex is immunoprecipitated by a polyclonal anti-human/ ~ integrin subunit antibody. In contrast, astrocytes, the other major glial cell type in brain, express multiple integrins including c~1/~, ~3/~1, and cts/~l complexes that are immunologically and electrophoretically indistinguishable from integrins expressed by rat fibroblasts. The/3 subunit of the oligodendrocyte integrin (/3OL) and rat fibroblast/~1 have different electrophoretic mobilities i
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Stimulation of in vitro myelin synthesis by microglia.
Glia, 1994Co-Authors: Steven P. Hamilton, Leonard H. RomeAbstract:Central nervous system myelin is elaborated by oligodendrocytes, which have been studied extensively in cell culture. Dissociated brain cultures allow in vitro analysis of events in Myelinogenesis, including cell-cell interactions. Microglia, the primary phagocytic cell of the central nervous system, appear in developing fiber tracts prior to the onset of myelination in vivo. To gain insight into potential oligodendrocyte-microglial interactions during development, these cells were co-cultured and various parameters of myelin synthesis were measured. In co-culture, microglia stimulated the synthesis of sulfatide, a myelin-specific galactolipid, in oligodendrocytes, as well as the expression of the myelin-specific proteins myelin basic protein and proteolipid protein. Activity of the oligodendrocyte cytoplasm-specific enzyme 2',3'-cyclic nucleotide 3'-phosphohydrolase was not elevated, suggesting that the effects of microglia were not due to stimulation of oligodendrocyte proliferation. This was confirmed by the inability of microglia to induce significant DNA synthesis. Conditioned medium from cultured microglia provided a similar stimulatory activity, suggesting that the increase in myelin synthesis does not require contact between oligodendrocytes and microglia. These findings suggest a stimulatory role for microglia during Myelinogenesis.
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Matrix interactions regulating Myelinogenesis in cultured oligodendrocytes.
Advances in experimental medicine and biology, 1990Co-Authors: Leonard H. Rome, Michael C. Cardwell, Phyllis N. Bullock, Steven P. HamiltonAbstract:Myelin is a membrane unique to the nervous system that is deposited in segments along selected nerve fibers. Myelin functions as an insulator to increase the velocity of impulses transmitted between the cell body of a nerve and its target. In the central nervous system (CNS) myelin is produced by oligodendroglial cells. Each cell extends numerous processes that ensheathe segments of several different axons simultaneously. A different mechanism of myelination appears to occur in the peripheral nervous system where Schwann cells myelinate only single segments of single axons. Other differences are seen between Schwann cells and oligodendroglia such as morphology, growth factor requirements, extracellular matrix involvement and composition of the myelin produced.
Juana M. Pasquini - One of the best experts on this subject based on the ideXlab platform.
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Transferrin and thyroid hormone converge in the control of Myelinogenesis
Experimental neurology, 2015Co-Authors: Leandro Nazareno Marziali, Corina I. García, Juana M. PasquiniAbstract:Abstract Myelination is a concerted mechanism tightly regulated in the brain. Although several factors are known to participate during this process, the complete sequence of events is far from being fully elucidated. Separate effects of apotransferrin (aTf) and thyroid hormone (TH) are well documented on rat myelin formation. TH promotes the maturation of oligodendrocyte progenitors (OPCs) into myelinating oligodendrocytes (OLGs), while aTf is able to induce the commitment of neural stem cells (NSCs) toward the oligodendroglial linage and favors OLG maturation. We have also demonstrated that Tf mRNA exhibited a seven-fold increase in hyperthyroid animals. These observations have led us to hypothesize that both factors may interplay during oligodendrogenesis. To assess the combined effects of aTf and TH on proper myelination in the rat brain, Tf expression and oligodendroglial maturation were evaluated at postnatal days 10 (P10) and 20 (P20) in several experimental groups. At P10, an up-regulation of both Tf mRNA and protein, as well as myelination, was found in hyperthyroid animals, while a decrease in Tf mRNA levels and myelin formation was detected in the hypothyroid group. At P20, no differences were found either in Tf mRNA or protein levels between hyperthyroid and control (Ctrol) rats, although differences in OLG differentiation remained. Also at P20, hypothyroid animals showed decreased Tf mRNA and protein levels accompanied with a less mature myelinating phenotype. Moreover, TH and aTf differentially regulate the expression of KLF9 transcription factor as well as TRα and TRβ at P10 and P20. Our results suggest that TH is necessary early in OLG development for aTf action, as exogenous aTf administration was unable to counteract the effect of low TH levels in the hypothyroid state in all the time points analyzed. Furthermore, the fact that hyperthyroidism induced an increase in Tf expression and aTf-dependent regulation of TRα strongly suggests that Tf could be involved in some of TH later effects on OLG maturation. Here we describe the possible relationship between TH and aTf and its implication in oligodendrogenesis.
Steven P. Hamilton - One of the best experts on this subject based on the ideXlab platform.
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Stimulation of in vitro myelin synthesis by microglia.
Glia, 1994Co-Authors: Steven P. Hamilton, Leonard H. RomeAbstract:Central nervous system myelin is elaborated by oligodendrocytes, which have been studied extensively in cell culture. Dissociated brain cultures allow in vitro analysis of events in Myelinogenesis, including cell-cell interactions. Microglia, the primary phagocytic cell of the central nervous system, appear in developing fiber tracts prior to the onset of myelination in vivo. To gain insight into potential oligodendrocyte-microglial interactions during development, these cells were co-cultured and various parameters of myelin synthesis were measured. In co-culture, microglia stimulated the synthesis of sulfatide, a myelin-specific galactolipid, in oligodendrocytes, as well as the expression of the myelin-specific proteins myelin basic protein and proteolipid protein. Activity of the oligodendrocyte cytoplasm-specific enzyme 2',3'-cyclic nucleotide 3'-phosphohydrolase was not elevated, suggesting that the effects of microglia were not due to stimulation of oligodendrocyte proliferation. This was confirmed by the inability of microglia to induce significant DNA synthesis. Conditioned medium from cultured microglia provided a similar stimulatory activity, suggesting that the increase in myelin synthesis does not require contact between oligodendrocytes and microglia. These findings suggest a stimulatory role for microglia during Myelinogenesis.
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Matrix interactions regulating Myelinogenesis in cultured oligodendrocytes.
Advances in experimental medicine and biology, 1990Co-Authors: Leonard H. Rome, Michael C. Cardwell, Phyllis N. Bullock, Steven P. HamiltonAbstract:Myelin is a membrane unique to the nervous system that is deposited in segments along selected nerve fibers. Myelin functions as an insulator to increase the velocity of impulses transmitted between the cell body of a nerve and its target. In the central nervous system (CNS) myelin is produced by oligodendroglial cells. Each cell extends numerous processes that ensheathe segments of several different axons simultaneously. A different mechanism of myelination appears to occur in the peripheral nervous system where Schwann cells myelinate only single segments of single axons. Other differences are seen between Schwann cells and oligodendroglia such as morphology, growth factor requirements, extracellular matrix involvement and composition of the myelin produced.
