Health & Medicine - Posted by Stephanie Desmon-JHU on Wednesday, July 11, 2012 14:24 - 0 Comments
Neuron insulators play surprising role in ALS
JOHNS HOPKINS (US) — Neuron-insulating cells unexpectedly turn out also to be critical for preventing neurodegenerative ailments like Lou Gehrig’s disease.
A research team found that a previously unknown function of the insulators—known as oligodendroglia—is to supply neurons with nutrition while the latter cells fire electrical signals around the brain and central nervous system.
Damage to the insulators appears to contribute to neurodegenerative diseases such as Lou Gehrig’s, the disorder associated with the Yankee hall of famer and formally known as amyotrophic lateral sclerosis, the researchers say.
Spinal cord cells in a mouse with ALS are producing little of the protein MCT1—as shown by the lack of lit-up cells—compared with those in a normal mouse. MCT1 is generated in the nervous system’s oligodendroglia cells, once thought to be mere insulators but proven now to have an important role both in feeding neurons and in preventing diseases like ALS. (Credit: Brett Morrison/Jeffrey Rothstein/JHU)
Straight from the Source
The discovery could lead to new strategies for treating ALS and other diseases that attack the body’s nerve fibers, such as multiple sclerosis, the researchers say. They published their findings online July 11 in the journal Nature.
“More than 100 years after their discovery, we have now found a fundamentally new property in the way oligodendroglia work in the brain, laying the foundation for a new approach to try to treat debilitating neurodegenerative diseases,” says Jeffrey D. Rothstein, the study’s leader.
“We’ve added a whole new category to what they do in the brain.”
Neurons transfer chemical and electrical signals around the body; the electrical transfer involves the movement of charges from neuron to neuron.
Axons, wire-like extensions of neurons, help move the messages from cell to cell, in some cases over many feet. Oligodendroglia insulate axons, like rubber coating around an electrical wire, to speed up the transmission of information.
Axonal death is a hallmark of ALS and most other neurodegenerative disorders, says Rothstein, professor of neurology and neuroscience at the Johns Hopkins University School of Medicine.
Other principal brain cells, the astroglia, had been believed to be primarily responsible for providing energy to neurons, in the form of glucose, Rothstein and his colleagues say.
Their experiments show, however, that oligodendroglia are surprisingly crucial in feeding neurons; they supply lactate, without which neurons and their axons die. The Johns Hopkins team says lactate appears to be far more important to nerve cell survival than previously thought.
Moreover, the protein MCT1, the dominant transporter of lactate in the brain, is only found in oligodendroglia, the team reports.
Link to ALS
Rothstein says the discovery was rooted in experiments during which scientists, using mice, knocked out the gene that makes the MCT1 protein and saw axons begin to die, even though they were still getting plenty of glucose.
As part of these experiments, the researchers engineered mice whose cells would light up if they were expressing MCT1. The scientists then determined that only oligodendroglia cells lit up, showing that MCTI is located on this type of cell alone.
They also knocked out the MCT1 in cell cultures and found that neurons would begin to die, but would recover when fed lactate, proving the importance of MCT1 in providing this nutritional compound. They conducted the same experiments in mice and got similar results.
Finally, the researchers turned their attention to ALS, a disease where they had recently uncovered abnormalities related to oligodendroglia. In mice with ALS, they found that MCT1 was missing in brain cells well before the disease developed; they found similar results in ALS patients. Rothstein says the findings suggest that oligodendroglia injury—specifically injury to the mechanism that produces MCT1—may be an important event in ALS onset and progression.
Rothstein says he hopes further research can establish that the activation of MCT1 in people will protect axons in those with ALS and other degenerative diseases.
The study was supported by the National Institutes of Health’s National Institute for Neurological Disorders and Strokes.
More news from Johns Hopkins: http://releases.jhu.edu