Public release date: 27-Jun-2007
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Contact: Emil Venere,
'Cars' imaging reveals clues to myelin damage
WEST LAFAYETTE, Ind. -- Researchers have discovered that calcium ions could play a crucial role in multiple sclerosis by activating enzymes that degrade the fatty sheath that insulates nerve fibers.
Learning exactly how the myelin sheath is degraded might enable scientists to determine how to halt disease progress and reverse damage by growing new myelin, said Ji-Xin Cheng, an assistant professor in Purdue University's Weldon School of Biomedical Engineering and Department of Chemistry.
"Although multiple sclerosis has been studied for many years, nobody knows exactly how the disease initially begins," he said. "The pathway is not clear."
Purdue researchers used an imaging technique called coherent anti-Stokes Raman scattering, or CARS, to study how the myelin sheath is degraded by a molecule called lysophosphatidylcholine, known as LPC. The LPC does not cause multiple sclerosis, but it is used extensively in laboratory research to study the deterioration of myelin, which insulates nerve fibers and enables them to properly conduct impulses in the spinal cord, brain and peripheral nervous system throughout the body.
The findings suggest that LPC causes sheath degradation by allowing an influx of calcium ions into the myelin. The increased concentration of calcium ions then activates two enzymes - calpain and cytosolic phospholipase A2 - which break down proteins and molecules in the myelin called lipids.
"It is possible that the same pathway causes myelin degradation in people suffering from multiple sclerosis and spinal cord injuries," Cheng said.
The research demonstrates that CARS microscopy is a valuable research tool and could become a future clinical method to diagnose multiple sclerosis and detect damage to the spinal cord from accident trauma, which also causes the myelin to degrade, he said.
Research findings are detailed in a paper appearing online this month in the Journal of Neuroscience Research. The paper was authored by biomedical engineering doctoral student Yan Fu and postdoctoral research associate Haifeng Wang; Terry B. Huff, a graduate teaching assistant in the Department of Chemistry; Riyi Shi, an associate professor of basic medical sciences in Purdue's School of Veterinary Medicine and an associate professor of biomedical engineering; and Cheng.
"The findings of this study will help us to identify key steps in the progression of the demyelination, which is a hallmark of multiple sclerosis," said Shi, a researcher at Purdue's Institute for Applied Neurology and Center for Paralysis Research. "This information will also facilitate the design of pharmaceutical interventions that slow down or even reverse the development of the debilitating disease."
The researchers used CARS to study and take images of healthy and diseased myelin. The researchers showed that an enzyme called cytosolic phospholipase A2 contributes to myelin degradation by snipping off one of the two tails that make up lipid molecules contained in the myelin. Cutting off one of the tails turns the lipid molecules into LPC, amplifying the effect and further degrading the myelin.
The research was carried out in spinal cord tissues extracted from animals and in the sciatic nerves of living mice.
Findings were confirmed by comparing CARS results with electron microscope images and measurements of electrical impulses in spinal cord tissue that distinguish between normal and diseased myelin.
CARS imaging takes advantage of the fact that molecules vibrate at specific frequencies. In a CARS microscope, two laser beams are overlapped to produce a single beam having a new frequency representing the difference between the original two beams. This new frequency then drives specific molecules to vibrate together "in phase," amplifying the signals from those molecules.
The research has been funded by the National Science Foundation and the National Institute of Biomedical Imaging and Bioengineering, with support from the state of Indiana and the Bindley Bioscience Center at Purdue's Discovery Park.
Future work will include a collaboration with researchers at Northwestern University to study how to regrow the myelin sheath in animals.
Writer: Emil Venere, (765) 494-4709, firstname.lastname@example.org
Sources: Ji-Xin Cheng, (765) 494-4335, email@example.com
Riyi Shi, (765) 496-3018, firstname.lastname@example.org
Related Web sites:
Ji-Xin Cheng: https://engineering.purdue.edu/BME/research/labs/cheng
Riyi Shi: http://lcme.vet.purdue.edu:8080/cgi-bin ... =21&DEPT=1
Weldon School of Biomedical Engineering: http://www.purdue.edu/bme
Abstract on the research in this release is available at: http://news.uns.purdue.edu/x/2007a/070627ChengCARS.html
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It is confusing and I am unsure how much calcium to take every day. Those of us that had years of steroids now have osteoporosis to contend with, so not taking additional calcium is a problem too.
Sure wish that someone knew the answers about taking calcium. This is a very grey problem area.
I think I should point out here that when a substance is found to be involved in causing the damage in M.S., or even if it's found to be beneficial, simply taking more or less of it isn't necessarily the right thing to do.
Everything we take into our bodies is metabolised – broken down, combined and recombined in order to play a useful, (or harmful), part in our daily functioning.
If it turns out that calcium is involved in damaging the myelin sheath, it's probable that the fault lies not in calcium itself but a failure in the way we process it; possibly because of a lack of vitamin D, possibly something as yet undiscovered.
As your experience has shown, calcium is a vital mineral for bone strength, but it's also an integral part of cellular function in the nervous system – it's when our bodies can't get rid of it quickly enough that the problems start.
Oxygen is a case in point: in the form of free radicals it's deadly to cells, but I wouldn't recommend reducing your intake!
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have been looking into ways to connect husband's drusen - these are hard, yellow deposits on optic nerve which block his peripheral vision- (he's had since childhood) and his MS.
Drusen are made up of calcium and lipid deposits. I posited that there might be a connection between his drusen and MS diagnosis. Neuro said no, but I continue to look into the calcium connection, and how LPC plays a role in both drusen and MS.
Here's a study on how vitamin E and anti-oxidants can inhibit LPC induced alterations.
http://www.liebertonline.com/doi/abs/10 ... alCode=ars
I appreciate your post stating "that the fault lies not in calcium itself but a failure in the way we process it; posibly because of a lack of vitamin D". In the research conducted by many Vitamin D experts, it is usually suggested that one take calcium with the Vitamin D. There are even studies that say without calcium, large doses of Vitamin D can cause harmful side effects. But, with calcium it does not. I totally agree - something as yet undiscovered in this process.
I'd never heard of drusen before, but coincidentally the paragraph below, which I've extracted from another thread, might have some bearing on the subject. My flimsy logic goes like this: too much sugar can affect sex hormones and unbalanced sex hormones may contribute to MS. Too much sugar also converts to lipid, so may be a step in the formation of drusen. This is complete guesswork on my part, but it looks like a similarity to me,
"Glucose and fructose are metabolized in the liver. When there’s too much sugar in the diet, the liver converts it to lipid. Using a mouse model and human liver cell cultures, the scientists discovered that the increased production of lipid shut down a gene called SHBG (sex hormone binding globulin), reducing the amount of SHBG protein in the blood. SHBG protein
plays a key role in controlling the amount of testosterone and estrogen..."
LPC has contradictory functions: it can activate RhoA and cause endothelial cells to tense up and open the gaps between them, thereby causing a leaking BBB, or it can do the opposite:
"Whereas LPC disrupts barrier function in naïve endothelium, it has a protective role when the barrier is leaky", (more information at: http://ajplung.physiology.org/cgi/conte ... 289/2/L174),
So I can certainly see where you're coming from with regards to a link between drusen and MS. I think it's an interesting possibility and worth looking into, but clearly your husband's neurologists disagrees… Ah well, I'll just have to learn to live with that…
sorry no time today to go hunting down refereed studies to support or challenge his claims7) Vitamin E as d-alpha tocopherol acetate of d-alpha tocopherol acid succinate. The latter is more practical since it is a pure form. Complex biochemical changes in the muscle tissue in chronic vitamin E deficiency are followed by histalogical lesions characteristic of muscular dystrophy. Deficiency has also been shown to produce demyelinization and distortion of the axon pattern in the spinal cord, giving rise to hypalgesia and progressive paresis. Fatal massive liver necrosis occurs in animals maintained on diets low in vitamin E and sulfur-containing amino acids; 800 international units before meals and bedtime must be adhered to in this treatment.
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