Loss of myelin – the insulating material around nerves – is the central feature of multiple sclerosis (MS). To explore early events in the development of MS, Subramaniam Sriram, M.B.B.S., William Whetsell, M.D., and colleagues have studied myelin loss using an animal model. In this model, intra-cerebral injection of lipopolysaccharide (LPS), an endotoxin component of the bacterial cell wall, is used to induce myelin loss.
The investigators reported in the journal Glia, that within hours of LPS injection, astrocytes (brain support cells) show reductions in gap junction proteins and glial fibrillary acid protein, key proteins that support oligodendrocytes (cells that make myelin). They also found that oligodendrocytes had fragmented DNA and expressed caspase 3, suggesting activation of programmed cell death pathways.
The findings suggest that the death of oligodendrocytes is an early event in the LPS model of demyelination and shows similarities to early events seen in MS. This model of oligodendrocyte loss should be useful for the development of novel therapeutics to rescue oligodendrocytes from death, which can be then explored in MS.
This research was supported by grants from the William Weaver Endowment and the Dr. West Family.
