Environmental changes, such as high temperatures and alterations in salt types and concentrations, trigger structural changes to myelin that may increase the risk of multiple sclerosis (MS), according to a new study.
The research, “Pathological transitions in myelin membranes driven by environmental and multiple sclerosis conditions,” was published in the journal Proceedings of the National Academy of Sciences of the USA (PNAS).
Efficient conduction of nerve impulses requires a healthy structure to myelin, the protective layer around nerve fibers.
A research team at Tel Aviv University had previously shown that myelin damage was associated with a structural change, one that altered myelin from a normal stack of thin layers to disease-related nano-scale tubes called inverted hexagonal shapes. This change resulted from altered lipid (fat) proportions and low content of myelin basic protein (MBP) — the key protein in myelin — resulting in pores spontaneously forming that increase susceptibility to an immune attack.
Aiming to further investigate environmental alterations that induce this structural change in myelin, the scientists used imaging techniques, such as X-ray scattering and cryogenic transmission electron microscopy, to track and measure myelin in healthy and diseased states in vitro (in the lab; outside of the body).
They first assessed the influence of replacing sodium with potassium, as both are needed to generate nerve impulses and to maintain body fluid balance. Then they analyzed the influence of calcium, as it plays a key role in neurotransmitter release from neurons; zinc, which regulates MBP; and magnesium, which affects nerve cell activity.
Results showed that ion type and concentration differentially affect the structure — in particular, cell and layer spacing — of both healthy and diseased myelin.
Researchers also showed that elevations in temperature had the same effect, inducing a gradual transition to nano-scale tubes structure at 42ºC (107.6ºF). MBP presence protected myelin layers from this structural transition at physiologically relevant temperatures.
“We have found that under certain environmental conditions, such as elevated salinity and temperature, myelin sheaths protecting neurons undergo structural transitions consistent with pathological myelin structures in multiple sclerosis,” Roy Beck, the study’s senior author, said in a press release.
“These small modifications create structural instabilities that allow the immune system to attack neurons,” Rona Shaharabani, the study’s first author, added.
Overall, the team concluded that “environmental conditions, such as buffer salinity and temperature, induce the same pathological phase transition as in the case of the lipid composition in the absence of MBP. These findings demonstrate that several local environmental changes can trigger pathological structural changes,” the researchers wrote.
They now are further investigating factors that induce changes in myelin structure. Existing candidates include “specific proteins and other alterations in the myelin’s fatty acids that are relevant, which may unravel further insights to fight multiple sclerosis and related disorders,” Shaharabani said.
Shaharabani added that the findings may help “explain the causes of MS and perhaps pave the way for a treatment or a cure.”
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