The brain is not a passive recipient of injury or illness. Research has shown that when neurons die and disrupt the natural flow of information they maintain with other neurons, the brain compensates by rerouting communication through other neural networks. This adjustment or rewiring will continue until the damage goes beyond compensation.
This adaptation process, a result of the brain’s plasticity or its ability to alter or reorganize neural networks, occurs in neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and Huntington’s (HD). As conditions progress, many genes change their normal expression, turning some genes up and others down. The challenge for researchers like Dr. Juan Botas, who studies Huntington’s disease, has consisted in determining which of the changes in gene expression are involved in causing the disease and which are helping to mitigate the damage, as this can be critical in developing effective therapeutic interventions.
In his laboratory at Baylor College of Medicine, Botas and colleagues are trying to understand what causes the loss of communication or synapses between neurons in Huntington’s disease. So far, research has focused on neurons because the normal huntingtin gene, the mutation of which is causing the disease, helps maintain healthy neuronal communication. In the current work, the researchers examined synapse loss in Huntington’s disease from a different perspective.
In this study, we focused on glial cells, which are a type of brain cell that is just as important to neural communication as neurons. We thought that glia might play a role in either contributing to or offsetting the damage seen in Huntington’s disease. One class of compensatory changes involved genes involved in synaptic function. Could Glia Be Involved? To answer this question, we created fruit flies that express mHTT only in glia, only in neurons, or in both cell types. To investigate whether reducing the expression of these genes in glia helped either disease progression or relief, we manipulated each gene in either neurons, glial cells, or both cell types in the HD fruit fly model. Then we determined the effect of the gene expression change on the functioning of the flies’ nervous system.
They assessed the health of the flies’ nervous system using an automated high-throughput system that quantified their movement behavior. The system filmed the flies as they naturally climbed a tube. Healthy flies climb easily, but when their mobility is impaired, the flies find it difficult to climb. The researchers looked at how the flies move because one of the characteristics of Huntington’s disease is the progressive disruption of normal body movements.
Our study shows that glia affected by Huntington’s disease respond by setting synapse genes, which has a protective effect. Some gene expression changes in Huntington’s disease promote disease progression, but other gene expression changes are protective. Our results suggest that combating all disease-related changes, such as using drugs to alter gene expression profiles, can counter the brain’s efforts to protect itself from this devastating disease. We suggest that researchers studying neurological disorders could deepen their analyzes by including glia in their studies.
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