'Cars' imaging reveals clues to myelin damage

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.

Source: Purdue University

Related stories:

Multiple Sclerosis: new MRI contrast medium enables early diagnosis in animal model
In an animal model of multiple sclerosis (MS), neuroradiologists and neurologists of the University hospitals of Heidelberg and Würzburg have been able to visualize inflammatory tissue damage, most of which had remained unrecognized up to now, with the aid of a new contrast medium, Gadofluorine M, in magnetic resonance imaging. The scientists have published their results in the online edition of the renowned medical journal Brain.
Statins have unexpected effect on pool of powerful brain cells
Cholesterol-lowering drugs known as statins have a profound effect on an elite group of cells important to brain health as we age, scientists at the University of Rochester Medical Center have found. The new findings shed light on a long-debated potential role for statins in the area of dementia.
Reprogramming Adult Stem Cells in the Brain
In recent years, stem cell researchers have become very adept at manipulating the fate of adult stem cells cultured in the lab. Now, researchers at the Salk Institute for Biological Studies achieved the same feat with adult neural stem cells still in place in the brain. They successfully coaxed mouse brain stem cells bound to join the neuronal network to differentiate into support cells instead.
Human stem cells show promise against fatal children's diseases
Scientists have used human stem cells to dramatically improve the condition of mice with a neurological condition similar to a set of diseases in children that are invariably fatal, according to an article in the June issue of the journal Cell Stem Cell.
Turning back the clock for Schwann cells
Myelin-making Schwann cells have an ability every aging Hollywood star would envy: they can become young again. According to a study appearing in the May 19 issue of the Journal of Cell Biology, David B. Parkinson (University College London, London, UK) and collogues have pinned down a protein that returns the cells to their youth, a finding that might help researchers understand why myelin production falters in some diseases.
Neuroscientists show anti-inflammation molecule helps fight MS-like disease
An immune system messenger molecule that normally helps quiet inflammation could be an effective tool against multiple sclerosis (MS). Neurology researchers led by Abdolmohamad Rostami, M.D., Ph.D., professor and chair of the Department of Neurology at Jefferson Medical College of Thomas Jefferson University and the Jefferson Hospital for Neuroscience in Philadelphia, have found that the protein interkeukin-27 (IL-27) helped block the onset or reverse symptoms in animals with an MS-like disease.
New research reveals critical knowledge about the nervous system
Uncover the neural communication links involved in myelination, the process of protecting a nerve’s axon, and it may become possible to reverse the breakdown of the nervous system’s electrical transmissions in such disorders as multiple sclerosis, spinal cord injuries, diabetes and cancers of the nervous system.
Simple eye scan opens window to multiple sclerosis
A five-minute eye exam might prove to be an inexpensive and effective way to gauge and track the debilitating neurological disease multiple sclerosis, potentially complementing costly magnetic resonance imaging to detect brain shrinkage - a characteristic of the disease’s progression.

News discussion:

Medicine & Health news