Myelin experimental allergic

P2 protein. PNS myelin contains a positively charged protein different from MBP that is referred to as P2 (Mr — 15,000). It is unrelated in sequence to MBP and is a member of a family of cytoplasmic fatty acid binding proteins (FABP) that are present in a variety of cell types [25]. The amount of P2 protein is variable among species, accounting for about 15% of total protein in bovine PNS myelin, 5% in humans and less than 1% in rodents. P2 protein is generally considered a PNS myelin protein but it is expressed in small amounts in CNS myelin sheaths of some species. P2 is an antigen for experimental allergic neuritis, the PNS counterpart of EAE (see Chs 36 and 38). P2 appears to be present in the major dense line of myelin sheaths, where it may play a structural role similar to MBP... 

Zhu J, Mix E, Olsson T, Link H (1994) Cellular messenger-Rna expression of interferon-gamma, 11-4 and transforming growth-factor-beta (Tgf-Beta) by rat mononuclear-cells stimulated with peripheral-nerve myelin antigens in experimental allergic neuritis. Clin Exp Immunol 98 306—312. 

EAE experimental allergic/autoimmune encephalitis is an animal model for demyelinating diseases, such as multiple sclerosis. It is induced by injection of myelin basic protein or whole CNS tissue together with adjuvants. 

Perry, L. L., Barzaga-Gilbert, E., and Trotter, J. L., T cell sensitization to proteolipid protein in myelin basic protein inducing relapsing experimental allergic encephalomyelitis. J. Neuroimmunol., 33, 7, 1991. 

Multiple sclerosis (MS) has traditionally been viewed as a disorder in which myelin is the primary target. However, there is recent evidence for abnormal SNS expression in experimental models of demyelination and in MS. Black et al (1999b) studied Na channel expression in the taiep rat, a mutant model in which myelin is initially formed normally, but then lost as a result of an oligodendrocyte abnormality. They observed the abnormal expression of SNS Na channel mRNA and protein in Purkinje cells following loss of myelin. More recently. Black et al (2000) demonstrated that SNS mRNA and protein, which are not detectable in normal Purkinje cells, are expressed within Purkinje cells in a mouse model of MS, chronic relapsing experimental allergic encephalomyelitis. Black et al (2000) have also demonstrated the expression of SNS mRNA (Fig. 7a, b) and protein (Fig. 7e, f) within cerebellar Purkinje cells from tissue obtained post-mortem from MS patients, but not in controls with no neurological disease (Fig. 7c, g). 

Experimental allergic encephalomyelitis (EAE). Autoimmune demyelinating disease induced in genetically susceptible mice, rats, or marmosets by immunization with myelin proteins or peptides. Animal model for multiple sclerosis. 

Experimental allergic encephalitis (EAE) obtained by injection of myelin basic protein (MBP)... 

In experiments on an animal model of experimental allergic neuritis, a demyelinating disease, treatment with Org 2766 protected the myelinated nerve fibers of the sural nerve from degeneration (Duckers et al., 1994), an action similar to that observed for lesions of the substantia nigra (see Section 6) and for sensory and glial cells in culture (see Section 7). 

The MBPS are a family of proteins. Unlike PLP, MBPs are easily extracted from the membrane and are soluble in aqueous solution. The major MBP has no tertiary structure and has a molecular weight of 15,000 Daltons. MBP is located on the cytoplasmic face of myelin membranes. Antibodies directed against MBPs elicit experimental allergic encephalomyelitis (EAE), which has become a model system for understanding multiple sclerosis, a demyelinating disease. A model of how PLP and MBPs aid in stabilizing myelin is shown in Figure 48.14. 

Kuchroo, V. K., Martin, C. A., Greer, J. M., Ju, S. T., Sobel, R. A., and Dorf, M. E. (1993) Cytokines and adhesion molecules contribute to the ability of myelin proteolipid protein-specific T cell clones to mediate experimental allergic encephalomyelitis. J. Immunol. 151, 4371-4382. 

In a model of immime-mediated de-myelination (chronic relapsing experimental allergic encephalomyelitis) it was noted that the BBB was disrupted not by altered TJ but by increased vesicular transport, which was associated with a metabolic change in the endothelial cells (Hawkins, Munro et al. 1992). In e qjerimental obstructive hydrocephalus, lanthanum tracer indicated that the TJ between ependymal cells in the ventricles allow paracellular transport of small solutes while restricting the movement of larger molecules (Nakagawa, Cervos-Navarro et al. 1985). 

Nagai, Y., Uchida, T, Takeda, S., and Ikuta, F., 1978, Restoration of activity for induction of experimental allergic peripheral neuritis by a combination of myelin basic protein P2 and gangliosides from peripheral nerve, Neurosci. Lett. 8 247-254. 

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