Updated 2:30 p.m. Thursday
Glial cells are critical to our body’s health—they support blood vessels, repair brain damage, and sense chemicals. Until the 1970s, scientists didn’t know what they were, and often had to wait for mice to die to investigate their function. But the increasing sophistication of molecular techniques have made many questions about these cells possible. In recent years, scientists have discovered that they may play a role in the body’s biological systems such as the immune system, tumor growth, and allergic response, or trigger inflammation.
Now, scientists have discovered a surprising and emerging role in inflammation of ongoing chronic pain—the impact of these cells on specific cells that line nerve tissue. The result shows that chronic pain may be the result of changes that happen during embryonic development, when embryonic neuron cells go into repair mode. In some ways, the discovery was equally as unexpected—rather than decades of advances in molecular techniques, it was the very lack of knowledge about the cells that made the discovery possible.
The study appears in the current online edition of Nature.
“Until then, we didn’t have a view on how glial cells interact with central nervous system,” said Arthur Liu, a professor of cell biology at Harvard Medical School and the study’s senior author. “This work shows you can actually manipulate glial cells in the brain to change the neurons themselves. We hope that this opens up new fields for research: how these cells can influence the biology of neurons, for example.”
Building upon earlier work done in Liu’s lab, the research team observed in experiments on mice that glial cells containing precursors of oligodendrocytes directly affect the expression of microtubules— the building blocks of nerve cells. Misfolding of microtubules in synapses between brain neurons increased by 19.2% in cortical glial oligodendrocytes versus control oligodendrocytes. Microtubules are key structural components of the nervous system, and expression of microtubule fibrils in neurons and glial oligodendrocytes has previously been found to lead to reduced function.
Ultimately, the researchers found that these changes led to reduced function in oligodendrocytes which happen to be the nerve-cell markers for chronic pain, though the research does not yet determine the connection between the glial cells and the pain.
Previous work by Liu’s team has established a connection between neurons and glial cells in the brain. “We have an understanding of how glial cells regulate different cells,” Liu said. “Now, we’re showing that we can directly manipulate some of those effects of glial cells in tissues and tissues of the nervous system.”
The study also suggests that in normal synapses, oligodendrocytes normally migrate and interact with other cells to improve health. “This is important because we have this process in brains,” Liu said.
The findings could be a long-term change in how scientists manage pain. Researchers may be able to use genetically modified glial cells to halt injuries. The development of such therapeutics could “become more of a reality,” Liu said.
Until now, scientists had thought glial cells replaced neurons rather than contributed to them in some manner. However, Liu’s findings show that glial cells in mice directly influence the integrity of cells that line nerve tissue. For Liu, that combination is evidence of both a signaling relationship between glial cells and neurons in the brain and a change in neuron function, and raises questions about the role of glial cells in nerve cell function.
Previous research from Liu’s lab has identified glial cells as contributing to nerve cell disease and aging. “This is an example of how glial cells are taking advantage of the primary cells that make up brain tissue,” he said.
The results of the study were funded by the National Institutes of Health, Parkinson’s Disease Foundation, the Jane Ellis Fund, the Burroughs Wellcome Fund, and the Blanche A. Moore Foundation.