Glia Brain Cells May Open Door to Treatment Strategy

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

Share this article:

Share article via email
An illustration shows a close-up view of the human brain inside a person's head.

Brain cells called glia work to protect the brain from damage in Huntington’s disease by reducing the expression of genes involved in maintaining connections between nerve cells, a new study indicates.

The findings suggest that targeting glia could be a useful strategy for Huntington’s treatment, and also highlight that not all changes in the brain that occur in Huntington’s are driving the disease.

The study, “Downregulation of glial genes involved in synaptic function mitigates Huntington’s disease pathogenesis,” was published in eLife.

Nerve cells, or neurons, are the brain cells that send electrical signals; this electrical activity controls many bodily processes and gives rise to thought and consciousness. Glia are another type of brain cell that generally has been less well-studied in the context of neurologic diseases. In people, there are several types of glia, each with specific functions, which include supporting neuronal health, helping to form connections between neurons, and fighting infections.

In the new study, a team of researchers conducted a series of analyses assessing the gene expression profiles of glia in models of Huntington’s. Gene expression, simply put, is the extent to which different genes are “turned on or off” in cells.

Recommended Reading
Banner for

My Experience Participating in an Observational Study

The researchers examined gene expression data from post-mortem human brain samples, as well as fly and mouse models of Huntington’s. By doing so, and by performing comparative analyses with gene expression data in other bodily tissues, the team identified hundreds of glia-specific genes that are altered in Huntington’s disease.

The team then conducted biological pathways analyses. In essence, they were trying to interpret the gene expression data within the context of cellular activity. A striking finding from this analysis was that, in Huntington’s, glia reduce the expression of genes related to synaptic assembly.

Synapses are the connections between neurons. When a neuron fires, it releases signaling molecules called neurotransmitters into the synapse, to pass the message along to the next neuron. Glia normally help to maintain these connections, but the data indicate this activity is reduced in Huntington’s.

Conceptually, there are two possible explanations for such a reduction in gene expression. On one hand, it is possible that the changes are disease-causing, as a result of underlying disease processes. On the other hand, it also is possible the change could be compensatory — a result of the brain trying to protect itself from ongoing damage caused by the disease.

“To investigate whether the reduction of expression of these genes in glia either helped with disease progression or with mitigation, we manipulated each gene either in neurons, glial cells or both cell types in the HD fruit fly model,” Juan Botas, PhD, said in a press release. Botas is a professor at Baylor College of Medicine in Houston, Texas, and co-author of the study.

Very broadly, the team found that reducing the activity of synaptic assembly genes protected flies from Huntington’s-like symptoms. This suggests that the reduction in expression of these genes is compensatory, not disease-causing.

In Huntington’s and other neurodegenerative diseases, synapses typically become damaged. As such, decreasing the synapse-supporting activity of glial cells might seem counterintuitive. But the researchers think this may be because, in Huntington’s, there is initially abnormally high neuronal growth very early in life. This leads to more neuronal connections in the brain than normal, which strains the system.

“The hyperfunction of a given brain region puts considerable strain on the circuit, and it seems that over the course of a lifetime, the brain keeps trying to compensate for the abnormalities that arise at different stages of [Huntington’s],” the researchers wrote.

In a broader context, this study highlights that biological changes that occur in the context of a disease are not necessarily acting to drive the disease, even if it might seem that way at first glance.

“Our findings suggest that antagonizing all disease-associated alterations, for example using drugs to modify gene expression profiles, may oppose the brain’s efforts to protect itself from this devastating disease,” Botas said.

The team also stressed the importance of including glia in studies of neurological disorders like Huntington’s.