"We suspect that the gene mutation contributes to Huntington's disease by reducing Kir4.1 levels in the astrocytes," said Sofroniew. "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," he added.
To test their hypothesis, the scientists explored what would happen if they artificially increased Kir4.1 levels inside the astrocytes. In one example, the results proved striking.
"Boosting Kir4.1 in the astrocytes improved the mice's ability to walk properly. We were surprised to see the length and width of the mouse's stride return to more normal levels," said Khakh. "This was an unexpected discovery."
"Our work breaks new ground by showing that disrupting astrocyte function leads to the disruption of neuron function in a mouse model of Huntington's disease," said Sofroniew. "Our findings suggest that therapeutic targets exist for the disorder beyond neurons."
While the results shed important light on one of the mechanisms behind Huntington's disease, the findings also offer more general implications, according to the authors
"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 UCLA team's next step will be to tease out the mechanism that reduces Kir4.1 levels and illuminate how this alters neuronal networks.
|Contact: Elaine Schmidt|
University of California - Los Angeles Health Sciences