Researchers Uncover New Knowledge About Astrocytes' Role In Huntington's Disease
Researchers at the UCLA Brain Research Institute are working on discovering new ways to prolong survival for those affected by Huntington's disease. The disease currently affects one in every 20,000 Americans. Industry experts believe that the research conducted at UCLA could potentially lead to a new drug for treating the disease. The researcher team has worked to boost the ability of a certain type of cell to absorb potassium in the brain. Certain changes in a cell's ability to absorb potassium led to improved motor function and higher rates of survival in mice with Huntington's disease. Dr. Baljit Khakh, who co-authored the study, said that the research was primarily focused on astrocytes, which are large, star-shaped cells found in the brain and spinal cord. Researches were working to discover how the Huntington mutation influenced astrocytes and what role astrocytes play in Huntington’s.
“Astrocytes…enable neurons [brain cells] to signal each other by maintaining an optimal chemical environment outside the cells,” said Khakh. “We used two mouse models to explore whether astrocytes behave differently during Huntington's disease.”
In the study, researchers implemented models that mimicked both an aggressive, early onset type of the disease and a slow-developing version. In both models, astrocytes with the mutant gene showed a drop of Kir4.1 — the protein that enables the cell to take in protein.
As UCLA Professor of Neurobiology, Michael Sonfroniew, says, "We suspect that the gene mutation contributes to Huntington's disease by reducing Kir4.1 levels in the astrocytes. This, in turn, reduces the cell's uptake of potassium. When excess potassium pools around neurons, they grow oversensitive and fire too easily, disrupting nerve-cell function and ultimately the body's ability to move properly. This may contribute to the jerky motions common to Huntington's disease." Boosting Kir4.1 in the astrocytes helped improve the mice’s ability to walk, Khakk says.
There is currently no cure for Huntington's disease, although multiple pharmaceutical companies are developing treatments, with varying success. Typically, patients live for 10 to 30 years after their initial diagnosis and suffer through losing physical and cognitive function. Dr. Khakh believes that focusing on astrocytes can potentially lead to new treatments for Huntington's disease.
“We're really excited that astrocytes can potentially be exploited for new drug treatments,” said Khakh. “Astrocyte dysfunction also may be involved in other neurological diseases beyond Huntington's.”
The results of the UCLA Brain Research Institute's study was published in the journal Nature Neuroscience and details the effects of boosting certain properties of astrocytes in mice.