Axonal damage is a major morphological alteration in the CNS of patients with multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). However, the underlying mechanism for the axonal damage associated with MS/EAE and its contribution to the clinical symptoms remain unclear. The expression of a fusion protein, named "Wallerian degeneration slow" (Wld s ), can protect axons from degeneration, likely through a ␤-nicotinamide adenine dinucleotide (NAD)-dependent mechanism. In this study, we find that, when induced with EAE, Wld s mice showed a modest attenuation of behavioral deficits and axon loss, suggesting that EAE-associated axon damage may occur by a mechanism similar to Wallerian degeneration. Furthermore, nicotinamide (NAm), an NAD biosynthesis precursor, profoundly prevents the degeneration of demyelinated axons and improves the behavioral deficits in EAE models. Finally, we demonstrate that delayed NAm treatment is also beneficial to EAE models, pointing to the therapeutic potential of NAm as a protective agent for EAE and perhaps MS patients.

Two strains of pink-pigmented, chlorine-resistant bacteria, GK101 and GK118, previously isolated from pink-colored microbial biomass occurring in a potable water treatment system were studied phylogenetically by using 16S rRNA gene sequence information. 16S ribosomal DNA (rDNA) fragments of approximately 1.5 kbp were amplified by the polymerase chain reaction (PCR) from crude cell lysates of the isolates and sequenced directly by a combined method consisting of linear PCR sequencing and automated fluorescence detection. Sequence comparisons and a phylogenetic tree analysis showed that the pink-pigmented isolates were closely related to Methylobacterium extorquens. Smaller fragments of 16S rDNA were also amplified from the bulk DNA extracted from the pink biomass, with a pair of PCR primers specific to the methylotrophs with the serine pathway or to proteobacteria of the alpha subclass. The PCR product was cloned by using the T-A cloning technique and sequenced as noted above. The results of this molecular approach suggested that bacteria phylogenetically the same as strain GK 101 predominated in the pink-pigmented population in situ and that some other bacteria of the genus Methylobacterium might also be involved in formation of the pink-colored aggregates.

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