PDGF-α Receptor and Myelin Basic Protein mRNAs Are Not Coexpressed by Oligodendrocytesin Vivo:A Doublein SituHybridization Study in the Anterior Medullary Velum of the Neonatal Rat

Butt, Arthur M.; Hornby, M. Fraser; Ibrahim, Merdol; Kirvell, Sara; Graham, Anthony; Berry, Martin

doi:10.1006/mcne.1996.0590

Cited by 41 publications

(30 citation statements)

References 49 publications

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“…Similarly, the AMV is a unique CNS tissue for studying axon-glial interactions in the adult Butt et al, 1995Butt et al, , 1998aButt et al, ,b, 1999Ibrahim et al, 1995) and during normal development (Butt et al, 1997a,b;Ibrahim, 1997;Hornby, 1999). Significantly, the AMV also lends itself to experimental manipulation, by injection of trophic factors (Butt et al, 1997c;Goddard et al, 1999) or demyelinating agents (Reynolds and Wilkin, 1993), by induction of experimental autoimmune encephalomyelitis (EAE; Raine and Dolich, 1986), and by midline lesions to induce axonal degeneration and regeneration (McConnell et al, 1984;Hutchinson and McConnell, 1990;Derouiche et al, 1994;Berry et al, 1998b). attaches laterally to the superior cerebellar peduncles on the dorsal surface of the pons.…”

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confidence: 96%

Oligodendrocytes and the control of myelination in vivo: new insights from the rat anterior medullary velum

Butt

Berry

2000

J. Neurosci. Res.

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The rat anterior medullary velum (AMV) is representative of the brain and spinal cord, overall, and provides an almost two-dimensional preparation for investigating axon-glial interactions in vivo. Here, we review some of our findings on axon-oligodendrocyte unit relations in our adult, development, and injury paradigms: (1) adult oligodendrocytes are phenotypically heterogeneous, conforming to Del Rio Hortega's types I-IV, whereby differences in oligodendrocyte morphology, metabolism, myelin sheath radial and longitudinal dimensions, and biochemistry correlate with the diameters of axons in the unit; (2) oligodendrocytes derive from a common premyelinating oligodendrocyte phenotype, and divergence of types I-IV is related to the age they emerge and the presumptive diameter of axons in the unit; (3) during myelination, axon-oligodendrocyte units progress through a sequence of maturation phases, related to axon contact, ensheathment, establishment of internodal myelin sheaths, and finally the radial growth and compaction of the myelin sheath; (4) we provide direct in vivo evidence that platelet-derived growth factor-AA (PDGF-AA), fibroblast growth factor (FGF-2), and insulin-like growth factor-I (IGF-I) differentially regulate these events, by injecting the growth factors into the cerebrospinal fluid of neonatal rat pups; (5) in lesioned adult AMV, transected central nervous system (CNS) axons regenerate through the putatively inhibitory environment of the glial scar, but remyelination by oligodendrocytes is incomplete, indicating that axon-oligodendrocyte interactions are defective; and (6) in the adult AMV, cells expressing the NG2 chondroitin sulphate have a presumptive adult oligodendrocyte progenitor antigenic phenotype, but are highly complex cells and send processes to contact axolemma at nodes of Ranvier, suggesting they subserve a specific perinodal function. Thus, axons and oligodendrocyte lineage cells form interdependent functional units, but oligodendrocyte numbers, differentiation, phenotype divergence, and myelinogenesis are governed by axons in the units, mediated by growth factors and contact-dependent signals.

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confidence: 96%

Oligodendrocytes and the control of myelination in vivo: new insights from the rat anterior medullary velum

Butt

Berry

2000

J. Neurosci. Res.

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“…3G-L). Because APC and PDGF␣R are not expressed at the same developmental stage of oligodendrocyte differentiation (Butt et al, 1997), we were able to avoid double counting of the cells. YFP-positive oligodendroglial cells were intermingled with the endogenous oligodendrocytes, suggesting good integration into the host spinal cord tissue.…”

Section: Preferential Differentiation Of Anpcs Along An Oligodendroglmentioning

confidence: 99%

Myelination of Congenitally Dysmyelinated Spinal Cord Axons by Adult Neural Precursor Cells Results in Formation of Nodes of Ranvier and Improved Axonal Conduction

Eftekharpour¹,

Karimi-Abdolrezaee²,

Wang³

et al. 2007

J. Neurosci.

101

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Emerging evidence suggests that cell-based remyelination strategies may be a feasible therapeutic approach for CNS diseases characterized by myelin deficiency as a result of trauma, congenital anomalies, or diseases. Although experimental demyelination models targeted at the transient elimination of oligodendrocytes have suggested that transplantation-based remyelination can partially restore axonal molecular structure and function, it is not clear whether such therapeutic approaches can be used to achieve functional remyelination in models associated with long-term, irreversible myelin deficiency. In this study, we transplanted adult neural precursor cells (aNPCs) from the brain of adult transgenic mice into the spinal cords of adult Shiverer (shi/shi) mice, which lack compact CNS myelin. Six weeks after transplantation, the transplanted aNPCs expressed oligodendrocyte markers, including MBP, migrated extensively along the white matter tracts of the spinal cord, and formed compact myelin. Conventional and three-dimensional confocal and electron microscopy revealed axonal ensheathment, establishment of paranodal junctional complexes leading to de novo formation of nodes of Ranvier, and partial reconstruction of the juxtaparanodal and paranodal molecular regions of axons based on Kv1.2 and Caspr (contactin-associated protein) expression by the transplanted aNPCs. Electrophysiological recordings revealed improved axonal conduction along the transplanted segments of spinal cords. We conclude that myelination of congenitally dysmyelinated adult CNS axons by grafted aNPCs results in the formation of compact myelin, reconstruction of nodes of Ranvier, and enhanced axonal conduction. These data suggest the therapeutic potential of aNPCs to promote functionally significant myelination in CNS disorders characterized by longstanding myelin deficiency.

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“…We have found that PDGF-AA delayed oligodendrocyte differentiation and axonal myelination. Because Rip1 cells do not express PDGF-aR in the AMV (Butt et al, 1997a), PDGF-AA almost certainly acted to arrest the differentiation of earlier stages of the oligodendrocyte lineage, which do express PDGF-aR in vivo (Ellison and de Vellis, 1994;Nishiyama et al, 1996a). The results Fig.…”

Section: Discussionmentioning

confidence: 71%

“…Because Rip1 promyelinating oligodendrocytes do not express PDGF-aR in the AMV (Butt et al, 1997a) and GC1 prooligodendrocytes express PDGF-aR only very rarely in vivo (Ellison and DeVellis, 1994), it is clear that PDGF-AA must have acted on either NG21 precursors or O41 preoligodendrocytes, both of which express PDGF-aR protein or mRNA in vivo (Ellison and de Vellis, 1994;Nishiyama et al, 1996a). The process by which oligodendrocyte recruitment was blocked in the AMV is unknown.…”

Section: Discussionmentioning

confidence: 97%

“…Nishiyama et al (1996a) observed coexpression of NG2 and PDGF-aR in oligodendrocyte precursors in vivo in the newborn rat brain by double immunolabelling, and Ellison and de Vellis (1994) showed, by combined in situ hybridization and immunohistochemistry, that PDGF-aR mRNA is expressed in O41 preoligodendrocytes but only rarely in GC1 prooligodendrocytes. In a double in situ hybridization study (Butt et al, 1997a), we showed that MBP mRNA-expressing promyelinating oligodendrocytes do not express PDGF-aR mRNA in vivo in the developing rat anterior medullary velum (AMV).…”

Section: Introductionmentioning

confidence: 99%

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Platelet-derived growth factor delays oligodendrocyte differentiation and axonal myelination in vivo in the anterior medullary velum of the developing rat

et al. 1997

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The AA dimeric form of platelet-derived growth factor (PDGF-AA) is implicated in the differentiation of cells of the oligodendrocyte lineage, which express PDGF receptors of the alpha subunit type (PDGF-alphaR). In the present study, we show that a single injection of PDGF-AA into the cerebrospinal fluid of neonatal rats delays oligodendrocyte differentiation and interrupts the progress of myelination in the anterior medullary velum (AMV), a white matter tract roofing the IVth ventricle of the brain. PDGF-AA or saline was injected intrathecally in postnatal day (P) 7 rats, and the AMV was subsequently removed and immunolabelled with the oligodendrocyte-specific antibody Rip, at P9, P12, and P21, corresponding to postinjection days (PID) 2, 5, and 14. At P9 (PID2), myelination was retarded in PDGF-AA-treated rats as opposed to saline-treated controls but progressed rapidly after P12 (PID5). Quantification supported the qualitative observations that PDGF-AA mediated an acute decrease in the number of Rip+ oligodendrocytes at P9-12, which largely recovered by P21, suggesting that PDGF-AA may have delayed recruitment of myelinating oligodendrocytes. However, the definitive number of Rip+ oligodendrocytes in the AMV was not increased, suggesting that its action as a promoter of early oligodendrocyte survival may not ultimately affect the definitive number of myelinating oliogdendrocytes in vivo. We discuss the possibilities that excess PDGF-AA may have acted on early oligodendrocytes (precursors or preoligodendrocytes) to either (1) delay their differentiation by maintaining them in the cell cycle or (2) accelerate their differentiation, which may result in premature cell death in the absence of synchronised survival signals. This study supports a role for PDGF-AA in the timing of oligodendrocyte differentiation in vivo, as has been shown in vitro.

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PDGF-α Receptor and Myelin Basic Protein mRNAs Are Not Coexpressed by Oligodendrocytesin Vivo:A Doublein SituHybridization Study in the Anterior Medullary Velum of the Neonatal Rat

Cited by 41 publications

References 49 publications

Oligodendrocytes and the control of myelination in vivo: new insights from the rat anterior medullary velum

Oligodendrocytes and the control of myelination in vivo: new insights from the rat anterior medullary velum

Myelination of Congenitally Dysmyelinated Spinal Cord Axons by Adult Neural Precursor Cells Results in Formation of Nodes of Ranvier and Improved Axonal Conduction

Platelet-derived growth factor delays oligodendrocyte differentiation and axonal myelination in vivo in the anterior medullary velum of the developing rat

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