Chemical Pathology of Diseases Involving Myelin

Norton, William T.; Cammer, Wendy

doi:10.1007/978-1-4757-1830-0_11

Cited by 25 publications

(15 citation statements)

References 158 publications

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“…In contrast, nerve conduction velocity is sometimes normal, and signs of peripheral neuropathy and demyelination are often absent (Kolodny and Fluharty, 1995). The reason for the differences between early-and lateonset forms of MLD might be the very low myelin lipid turnover after the initial formation of myelin (Norton and Cammer, 1984). CGT/ASA(Ϫ/Ϫ) developed tremor of the head, ataxia, and weakness of hindlimbs and forelimbs, but we did not find indications for demyelination or peripheral neuropathy.…”

Section: Cortical Hyperexcitability In Asa(؊/؊) Micecontrasting

confidence: 60%

Sulfatide Storage in Neurons Causes Hyperexcitability and Axonal Degeneration in a Mouse Model of Metachromatic Leukodystrophy

Eckhardt

Hedayati²,

Pitsch³

et al. 2007

J. Neurosci.

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Section: Cortical Hyperexcitability In Asa(؊/؊) Micecontrasting

confidence: 60%

Sulfatide Storage in Neurons Causes Hyperexcitability and Axonal Degeneration in a Mouse Model of Metachromatic Leukodystrophy

Eckhardt

Hedayati²,

Pitsch³

et al. 2007

J. Neurosci.

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“…In nonneuronal tissues, it has been proposed that apoE helps to mobilize lipids and to mediate the transport of cholesterol from peripheral tissue to the central vascular pool (28,29,33). In the nervous system, cholesterol is a major by-product of the degeneration of myelinated axons (34). We hypothesize that following injury, phagocytosis of degenerating axons and myelin stimulates an increase in the synthesis and secretion of apoE by reactive FIG.…”

Section: Discussionmentioning

confidence: 90%

Nerve injury stimulates the secretion of apolipoprotein E by nonneuronal cells.

Snipes¹,

McGuire²,

Norden³

et al. 1986

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

229

108

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Nerve trauma initiates significant changes in the composition of proteins secreted by nonneuronal cells. The most prominent of these proteins is a 37-kDa protein, whose expression correlates with the time course of nerve development, degeneration, and regeneration. We now report that the 37-kfla protein is apolipoprotein E (apoE). We produced a specific antiserum against the 37-kDa protein isolated from previously crushed nerves. This antiserum recognizes a 36-kDa protein in rat serum that we have purified and identified as apoE. The anti-37-kDa antiserum also recognizes apoE on electrophoretic transfer blots of authentic samples of high and very low density lipoproteins. The nerve 37-kDa protein comigrates with apoE by two-dimensional electrophoresis, shares a similar amino acid composition, and reacts with an antiserum against authentic apoE. The purified apoE specifically blocks the immunoprecipitation of [35S~methionine-labeled 37-kDa protein synthesized by nonneuronal cells. Thus, on the basis of its molecular mass, isoelectric point, amino acid composition, and immunological properties, we conclude that the 37-kDa protein is apoE. We also used light microscopic immunohistochemistry to localize apoE following nerve n'jury. In rats with optic nerve lesions, the 37-kDa antiserum bound specifically to the degenerating optic tracts and to the retinorecipient layers of the lateral geniculate nucleus and the superior colliculus. We propose that apoE is synthesized by phagocytic cells in response to nerve injury for the purpose of mobilizing lipids produced as a consequence of axon degeneration.Nonneuronal cells in the mammalian nervous system are estimated to outnumber neurons by 10:1 and may account for nearly half of the volume of the brain (1). Although the functions of some nonneuronal cells [which include astrocytes, oligodendrocytes, and microglia in the central nervous system (CNS) and Schwann cells in the peripheral nervous system (PNS)] are beginning to be understood, thus far little is known at the molecular level of the roles such cells play in the development and in the normal functioning of the nervous system or in response to injury. Recently, it has been shown that nonneuronal cells in the PNS and CNS release soluble proteins into their microenvironment during development (2-4) and following nerve injury (3-5). The fact that the synthesis and secretion of some of these proteins is significantly enhanced during nerve regeneration in the PNS leads naturally to the hypothesis that they may play an important role in determining the ability of an axon to regenerate following injury. The poor regenerative response of most CNS neurons in higher vertebrates might be related to the failure of CNS nonneuronal cells to secrete the requisite proteins necessary for regeneration or the failure to secrete them in sufficient amounts. These considerations serve to emphasize the importance of identifying and characterizing the proteins released by nonneuronal cells in the PNS and CNS and of elucidating how t...

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“…In EAE, macrophages actively strip the myelin lamellae, with the appearance of myelin debris within the macrophage cell body (Lampert and Carpenter, 1965). An increase in cholesterol ester levels in the CNS of both MS and EAE is the result of esterification of myelin cholesterol by phagocytic cells immediately following ingestion of myelin (Maggio et al, 1972;Norton and Cammer, 1984). Little or no CE is found in normal, healthy CNS.…”

Section: Introductionmentioning

confidence: 99%

EAE cerebrospinal fluid augments in vitro phagocytosis and metabolism of CNS myelin by macrophages

Sommer

Forno

Smith

1992

J of Neuroscience Research

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Previous studies from this laboratory have shown that CNS myelin is phagocytized and metabolized by cultured rat macrophages to a much larger extent when myelin is pretreated with serum containing antibodies to myelin constituents than when it is left untreated or pretreated with non-specific serum. In this study the effect of cerebrospinal fluid (CSF) from rabbits with experimental allergic encephalomyelitis (EAE) in promoting myelin phagocytosis was examined. Fourteen rabbits were immunized with purified myelin in Freund's complete adjuvant, seven of which developed clinical EAE symptoms. Serum and CSF were collected from EAE and control rabbits, and the CSF was centrifuged to remove cells. Sera and CSF from these rabbits and from Freund's adjuvant-immunized controls and untreated controls were measured for IgG content by radial diffusion assay, their myelin antibody characteristics were analyzed by immunoblots, and the ability of these serum and CSF samples to promote myelin phagocytosis when used for myelin opsonization was examined. The ability of a CSF sample to enhance radioactive myelin uptake and phagocytosis by cultured macrophages as measured by the appearance of radioactive cholesterol ester was linearly proportional to its total IgG titer, and correlated approximately both with clinical symptoms of the animal and the presence of antibody against the myelin constituents myelin basic protein, proteolipid protein, and galactocerebroside. The cholesterol esterification activities of EAE sera correlated to a lesser extent with IgG levels and clinical symptoms. These results suggest a possible role for CSF-localized anti-myelin antibody in demyelination in the CNS by macrophages in EAE, and they encourage further study of the role of CSF antibody in cell-mediated demyelination in multiple sclerosis.

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Chemical Pathology of Diseases Involving Myelin

Cited by 25 publications

References 158 publications

Sulfatide Storage in Neurons Causes Hyperexcitability and Axonal Degeneration in a Mouse Model of Metachromatic Leukodystrophy

Sulfatide Storage in Neurons Causes Hyperexcitability and Axonal Degeneration in a Mouse Model of Metachromatic Leukodystrophy

Nerve injury stimulates the secretion of apolipoprotein E by nonneuronal cells.

EAE cerebrospinal fluid augments in vitro phagocytosis and metabolism of CNS myelin by macrophages

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