Sci. Aging Knowl. Environ., 31 August 2005
Bone marrow cells deaden neurons in diabetes
R. John Davenporthttp://sageke.sciencemag.org/cgi/content/full/2005/35/nf70
Like bullies who move into peaceful neighborhoods and cause trouble, bone marrow cells fuse with and short-circuit neurons in diabetic rodents, new work reveals. The findings uncover a new trigger for diabetes-related nerve damage and suggest that diverting the errant bone marrow cells might alleviate the complication.
In diabetes, nerves often deteriorate or die, a condition known as neuropathy. Scientists have hypothesized that rising sugar concentrations inside neurons cause protein damage that destroys nerve cells, but diabetes researcher Lawrence Chan of Baylor College of Medicine in Houston, Texas, and colleagues suspected that something else might contribute. Previously, the researchers found that in diabetic animals, some bone marrow cells start producing the glucose-regulating hormone insulin and infiltrate organs throughout the body. The researchers want to exploit these cells to alleviate diabetes, but they wondered whether the roving cells might also exacerbate complications of diabetes, including nerve problems.
To investigate whether bone marrow cells invade nerves, the team fed rats a diabetes-inducing drug. Then, they scrutinized the animals' sciatic nerves and dorsal root ganglia, spinal cord structures where sensory nerves converge. Nerves signaled sluggishly, an indicator of neuropathy. About 10% of neurons in the dorsal root ganglion produced proinsulin, an insulin precursor. In addition, these cells bore a protein characteristic of bone marrow cells. Nerves in nondiabetic rats didn't carry either molecule, raising the possibility that diabetes spurs bone marrow cells to travel to nerves and join with neurons.
To test this idea, the team performed bone marrow transplants in mice. They removed bone marrow cells from animals that carried a marker protein and injected them into rodents without the molecule. After inducing diabetes in some animals, the scientists found that proinsulin-making neurons also carried the donor's marker protein. Nondiabetic mice did not show the bone marrow indicator in their nerves.
Further studies suggest that the bone marrow-neuron fusions malfunction. Proinsulin-producing neurons from diabetic rats held too much calcium, and these cells were more likely to commit suicide than were normal neurons from either diabetic or nondiabetic animals. Chan says that the fusion of bone marrow cells and neurons "is an important new mechanism" in neuropathy, but he doesn't know why the cells fuse or how that event causes nerve damage.
"It's extremely novel, and for that reason, it's exciting," says neurologist Eva Feldman of University of Michigan, Ann Arbor. However, she notes that rodent lines vary in susceptibility to neuropathy, and the researchers showed that rats get neuropathy and that mice have fused cells. Now, they need to show neuropathy and cell fusion in the same animals. "It's a very solid piece of work," says endocrinologist Paul Thornalley of Essex University in United Kingdom. The study calls into question the wisdom of using these bone marrow cells to fight diabetes because they could harm nerves, he says. Next, researchers should look for signs of similar fusions in diabetes patients, Thornalley says. If they turn up, disciplining the cells might restore order.
August 31, 2005
Science of Aging Knowledge Environment. ISSN 1539-6150