Models of MS

Notes The bacterial MS channels, MscL and MscS, are the only MS channel proteins whose 3-D structure has been determined. The gating mechanism and/or physiologic function of some MS channels have not been characterized fully. Note that in contrast to the bilayer mechanism, no single experimental result provides direct support for the tethered model of MS channel gating (1). NT indicates that the effect of amphipaths (CPZ and TNP) has not been tested in the particular type of MS channels (adopted from Reference 10, with permission). 

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). 

THC and other cannabinoids have been shown (Baker et al. 2000) to improve both tremor and spasticity in a well-validated animal model of MS (experimental allergic encephalomyelitis). Antagonism of the CB j receptor aggravated these signs, indicating a role for endogenous cannabinoids in the control of tremor and spasticity. 

Additional evidence that links NO with MS can be found in the animal model of MS, experimental autoimmune encephalomyelitis (EAE). iNOS mRNA has been detected in EAE rat brain tissue (Koprowski etal.,1993) and NO produced by inflammatory cells complexes with iron-sulfur proteins in spinal cords (reviewed by Merrill and Murphy, 1995). Also, Cross et al. 

Exposure to helminths inhibits central nervous system inflammation in experimental autoimmune encephahtis (EAE). a rodent model of MS. Exposure of mice to viable S. mansoni or dead (freeze-thawed) S. mansoni s protects from EAE. Schistosome exposure reduces proinflammatory IL12/23p40, IFNy and TNFa and promotes r ulatory TGPp, ILIO and IL4 expression by splenocytes and CNS immune cells. Protection against EAE appears to require intact IL4 signaling. ... 

MS/MS analysis of DBS is one model of clinical analysis that has been utilized on millions of infants for 15 years. Each year since its first clinical use in the mid-1990s, there have been substantial improvements such as improved ionization, more sensitive instruments, and a reduction of the actual size of instruments. The profile has expanded to include T4, succinylacetone, and in a few labs, LSD metabolites and steroids. Many of these analyses can be used in other clinical applications and research such as nutrition studies in premature infants or postmortem screening on sudden unexplained deaths in infants or carnitine status in dialysis patients with end-stage renal disease. As additional clinical assays are developed and used, it might be wise for these labs to consider the models of MS/MS, NBS, and the DBS as a reference. 

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