Experimental allergic encephalomyelitis: Characterization of T lymphocytes that bind myelin basic protein and synapsin

Santis, M. L. De; Roth, German A.

doi:10.1002/jnr.490430106

Cited by 11 publications

(7 citation statements)

References 33 publications

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“…Similar to the pattern observed for MBP, CN-Pase activity showed a reduction of about 40% in Groups I1 and V, but in the treated Groups 111 and IV it maintained a value matching that of control rats. Quantitation of a synaptosomal protein, synapsin, immunologically related to MBP (Pedraza et al, 1988;De Santis et al, 1992;De Santis and Roth, 1996), however, failed to demonstrate significant differences among the groups of animals analyzed, although a tendency to decrease was observed in rats from Group 11, IV, and V. These changes occurred without significant changes in the amount of total protein per gram of brain among all groups of animals. However, sick animals from Groups I1 and V showed decreased amounts of brain cerebrosides and total cholesterol and increased levels of esterified cholesterol but a normal quantity of sulfatides (Fig.…”

Section: Biochemical Alterationsmentioning

confidence: 85%

Experimental autoimmune encephalomyelitis: Antigen-induced inhibition of biochemical and immunohistological alterations

et al. 1996

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A comprehensive biochemical, immunological, and histological study was undertaken during suppression of experimental autoimmune encephalomyelitis (EAE) induced by antigen‐specific inhibition of the immune response. Pretreatment of Wistar rats by intraperitoneal administration of low doses of saline‐soluble bovine myelin or myelin basic protein (MBP) but not with ovalbumin suppresses the appearance of the clinical symptoms of EAE induced by sensitization with bovine myelin in complete Freund's adjuvant. Analysis of the central nervous system (CNS) of animals pretreated with MBP or whole myelin shows inhibition of the diminution of MBP and 2′,3′‐cyclic nucleotide 3′‐phosphohydrolase (CNPase) activity observed in the EAE animals or in rats pretreated with ovalbumin. With respect to the CNS lipid content, these suppressive treatments abolish the increase in esterified cholesterol and partially revert the diminution in the content of cerebrosides and total cholesterol characteristic of the acute stage of the disease. Concomitantly, meningeal and parenchymal infiltration with mononuclear cells and deposits of immunoglobulins in the infiltrated regions as well as in spinal cord motor neurons were reduced. Analysis of the humoral response to myelin antigens shows that all EAE as well as treated animals developed antibodies to MBP and other myelin proteins. However, a higher incidence and level of these antibodies was observed in nontreated EAE animals and MBP‐ and ovalbumin‐treated rats, while rats treated with total bovine myelin showed a highly reduced humoral response. The present results indicate that intraperitoneal treatment with soluble forms of myelin antigens, concomitant with the suppression of the clinical symptoms of the disease, markedly reduces the biochemical and histological alterations occurring in EAE animals and produces changes in the autoimmune humoral response. © 1996 Wiley‐Liss, Inc.

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Section: Biochemical Alterationsmentioning

confidence: 85%

Experimental autoimmune encephalomyelitis: Antigen-induced inhibition of biochemical and immunohistological alterations

et al. 1996

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“…50 On the other hand, it has been reported that both anti-MBP antibody and MBP-specific T cells can crossreact with synapsin I, 51,52 and the presence of synapsin I-crossreacting T cells correlated with clinical EAE signs. 53 Therefore, autoimmunity is another possibility for the presynaptic structure damage in EAE. However, this mechanism seems less relevant to the loss of postsynaptic PDS-95.…”

Section: Discussionmentioning

confidence: 99%

Dendritic and Synaptic Pathology in Experimental Autoimmune Encephalomyelitis

Zhu

Luo

Moore

et al. 2003

The American Journal of Pathology

110

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Evidence has shown that excitotoxicity may contribute to the loss of central nervous system axons and oligodendrocytes in multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Because dendrites and synapses are vulnerable to excitotoxicity, we examined these structures in acute and chronic models of EAE. Immunostaining for microtubule-associated protein-2 showed that extensive dendritic beading occurred in the white matter of the lumbosacral spinal cord (LSSC) during acute EAE episodes and EAE relapses. Retrograde labeling confirmed that most motoneuron dendrites were beaded in the white matter of the LSSC in acute EAE. In contrast, only mild swelling was observed in the gray matter of the LSSC. Dendritic beading showed marked recovery during EAE remission and after EAE recovery. In addition, synaptophysin, synapsin I, and PSD-95 immunoreactivities were significantly reduced in both the gray and white matter of the LSSC during acute EAE episodes and EAE relapses, but showed partial recovery during EAE remission and after EAE recovery. Pathologically, both dendritic beading and the reduction in synaptic protein immunoreactivity were well correlated with inflammatory cell infiltration in the LSSC at different EAE stages. We propose that dendritic and synaptic damage in the spinal cord may contribute to the neurological deficits in EAE. Central nervous system (CNS) inflammation and neurodegeneration are two major pathological processes in multiple sclerosis (MS). Understanding the pathology and mechanisms of CNS degeneration in MS is essential for protecting neural structures and functions in MS patients. In addition to the demyelination and the loss of oligodendrocytes, axonal degeneration in MS has received substantial attention. It has been realized that axonal loss starts early in the disease course, 1,2 and that the accumulation of axonal damage parallels in general the progressive neurological dysfunction in MS patients.3

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“…In this study, the oral tolerance induced by LTBSC resulted of benefit in the event of development of an immune response to myelin antigens. We have previously found that affinity‐purified antibodies and certain T‐lymphocyte populations specific for MBP present in EAE animals can also recognize synapsin among several neuronal proteins (Pedraza et al, 1988; De Santis et al, 1992; De Santis and Roth, 1996; Slavin et al, 1996). We also evaluated whether the same T cell derived from EAE animals can recognize MBP and synapsin via recognition by the T‐cell receptor.…”

Section: Discussionmentioning

confidence: 99%

“…We have previously demonstrated in rats with EAE the existence of anti‐MBP antibodies and T cells that are able to recognize the neuronal protein synapsin (Pedraza et al, 1988; De Santis et al, 1992). These cells are specific for the EAE animals, and they correlate with the disease clinical signs (De Santis and Roth, 1996). The human T‐cell response against synapsin has also been characterized in patients with MS (Polak et al, 2001).…”

mentioning

confidence: 99%

Protective effect of a synapsin peptide genetically fused to the B subunit of Escherichia coli heat‐labile enterotoxin in rat autoimmune encephalomyelitis

Scerbo

Rupil

Bibolini

et al. 2009

J of Neuroscience Research

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Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease with similarities to multiple sclerosis that requires the activation of auto reactive T cells that infiltrate the central nervous system. In previous studies we have shown that intraperitoneal administration of synaptosomal antigens could suppress EAE. Herein we examined the effect in this animal model of a fusion protein comprising the C domain of synapsin Ia and the B subunit of Escherichia coli heat-labile enterotoxin (LTBSC). Oral administration to rats of low amounts of LTBSC induced immunological systemic tolerance to the encephalitogenic myelin basic protein. Treatment with LTBSC prior to EAE induction diminished disease incidence, DTH reaction to myelin basic protein, and central nervous system inflammation. LTBSC treatment also reduced the specific T-cell proliferative response to myelin basic protein, decreased nitric oxide production, and augmented arginase activity by peritoneal macrophages. All animals challenged for EAE developed antibody response specific for myelin basic protein, but rats treated with LTBSC showed a lower IgG2b/IgG1 ratio, indicating a shift to a Th2-type milieu. The data presented here suggest that well-conserved synapsin peptides conjugated to the B subunit of enterotoxins from the cholera toxin family have a protective role and provide a potential therapeutic tool for intervention in EAE as well as in multiple sclerosis.

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Experimental allergic encephalomyelitis: Characterization of T lymphocytes that bind myelin basic protein and synapsin

Cited by 11 publications

References 33 publications

Experimental autoimmune encephalomyelitis: Antigen-induced inhibition of biochemical and immunohistological alterations

Experimental autoimmune encephalomyelitis: Antigen-induced inhibition of biochemical and immunohistological alterations

Dendritic and Synaptic Pathology in Experimental Autoimmune Encephalomyelitis

Protective effect of a synapsin peptide genetically fused to the B subunit of Escherichia coli heat‐labile enterotoxin in rat autoimmune encephalomyelitis

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