Columbia University Medical Center

In ALS, Relations Between Neurons and Neighbors Go Awry

New Columbia research is revealing that in ALS communication between cells call astrocytes (pictured) and motor neurons is "profoundly disrupted."

New Columbia research reveals that in ALS, communication between cells called astrocytes (pictured) and motor neurons is "profoundly disrupted." Photo: Neurorocker at en.wikipedia.

Although ALS is dubbed a disease of motor neurons, about five years ago Columbia researchers made a discovery that has since changed the course of ALS research.

Instead of causing their own demise as previously thought, motor neurons appear to be destroyed by neighboring glial cells in the brain and spinal cord, as revealed in two independent studies led by Tom Maniatis, PhD, chair of Biochemistry & Molecular Biophysics and Isidore S. Edelman Professor of Biochemistry, and Serge Przedborski, MD, PhD, Page & William Black Professor of Neurology.

After digging deeper into the cells’ relationship, researchers from Maniatis’s lab found that the motor neurons die when the communication between neurons and a type of glial cell called astrocytes is “profoundly disrupted” by the disease.

As described in a release from the ALS Association, altered communication between the cells

resulted in a network of gene changes that reduced protective behaviors for both types of cells and increased harmful activity by the astrocytes.

“These results strengthen the case that astrocytes are central to the ALS disease process,” said Lucie Bruijn, PhD, chief scientist for the ALS Association.

“Furthermore, the results are based on an exciting new disease model system, one that will allow us to test important hypotheses and search for new therapeutic targets.”

The study was made possible, in part, by the development of a new cell culture system that puts motor neurons and astrocytes in close proximity to each other, but not so close that they are impossible to untangle for later analysis.

Tracking the two cell types simultaneously allowed the investigators to observe, for the first time, how changes in each cell type influence changes in the other, the release reported.

The study was published Feb. 6 online in the Proceedings of the National Academy of Sciences.

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