Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A new approach to Huntington's disease?

31.03.2014

UCLA study discovers potassium boost improves walking in mouse model

Tweaking a specific cell type's ability to absorb potassium in the brain improved walking and prolonged survival in a mouse model of Huntington's disease, reports a UCLA study published March 30 in the online edition of Nature Neuroscience. The discovery could point to new drug targets for treating the devastating disease, which strikes one in every 20,000 Americans.

Huntington's disease is passed from parent to child through a mutation in the huntingtin gene. By killing brain cells called neurons, the progressive disorder gradually deprives patients of their ability to walk, speak, swallow, breathe and think clearly. No cure exists, and patients with aggressive cases can die in as little as 10 years.

The laboratories of Baljit Khakh, a professor of physiology and neurobiology, and Michael Sofroniew, a professor of neurobiology, teamed up at the David Geffen School of Medicine at UCLA to unravel the role played in Huntington's by astrocytes--large, star-shaped cells found in the brain and spinal cord.

"Astrocytes appear in the brain in equal numbers to neurons, yet haven't been closely studied. They enable neurons to signal each other by maintaining an optimal chemical environment outside the cells," explained Khakh, who, with Sofroniew, is a member of the UCLA Brain Research Institute. "We used two mouse models to explore whether astrocytes behave differently during Huntington's disease."

The first model mimicked aggressive, early-onset of the disorder, while the second imitated a slow-developing version.

Khakh and Sofroniew examined how the huntingtin mutation influenced astrocytes in the brain. In particular, they looked at astrocytes' interaction with a type of neuron that plays a central role in coordinating movement.

One key finding stood out from the data.

In both models, astrocytes with the mutant gene showed a measurable drop in Kir4.1, a protein that allows the astrocyte to take in potassium through the cell membrane. This left too much potassium outside the cell, disrupting the chemical balance and increasing the nearby neurons' excitability–or capacity to fire.

"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.

###

The study was supported by the CHDI Foundation, the National Institute of Mental Health and the National Institute of Neurological Disorders and Stroke.

Khakh and Sofroniew's coauthors included Xiaoping Tong, Yan Ao, Guido Faas, Ji Xu, Martin Haustein, Mark Anderson and Istvan Mody from UCLA; and Sinifunanya Nwaobi and Michelle Olsen from the University of Alabama at Birmingham.

Elaine Schmidt | EurekAlert!
Further information:
http://www.ucla.edu

Further reports about: Huntington's Huntington's disease UCLA aggressive astrocyte astrocytes disorder neurons potassium

More articles from Health and Medicine:

nachricht Real-time imaging of lung lesions during surgery helps localize tumors and improve precision
30.07.2015 | American Association for Thoracic Surgery

nachricht Experimental MERS vaccine shows promise in animal studies
29.07.2015 | NIH/National Institute of Allergy and Infectious Diseases

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Glaciers melt faster than ever

Glacier decline in the first decade of the 21st century has reached a historical record, since the onset of direct observations. Glacier melt is a global phenomenon and will continue even without further climate change. This is shown in the latest study by the World Glacier Monitoring Service under the lead of the University of Zurich, Switzerland.

The World Glacier Monitoring Service, domiciled at the University of Zurich, has compiled worldwide data on glacier changes for more than 120 years. Together...

Im Focus: Quantum Matter Stuck in Unrest

Using ultracold atoms trapped in light crystals, scientists from the MPQ, LMU, and the Weizmann Institute observe a novel state of matter that never thermalizes.

What happens if one mixes cold and hot water? After some initial dynamics, one is left with lukewarm water—the system has thermalized to a new thermal...

Im Focus: On the crest of the wave: Electronics on a time scale shorter than a cycle of light

Physicists from Regensburg and Marburg, Germany have succeeded in taking a slow-motion movie of speeding electrons in a solid driven by a strong light wave. In the process, they have unraveled a novel quantum phenomenon, which will be reported in the forthcoming edition of Nature.

The advent of ever faster electronics featuring clock rates up to the multiple-gigahertz range has revolutionized our day-to-day life. Researchers and...

Im Focus: Superfast fluorescence sets new speed record

Plasmonic device has speed and efficiency to serve optical computers

Researchers have developed an ultrafast light-emitting device that can flip on and off 90 billion times a second and could form the basis of optical computing.

Im Focus: Unlocking the rice immune system

Joint BioEnergy Institute study identifies bacterial protein that is key to protecting rice against bacterial blight

A bacterial signal that when recognized by rice plants enables the plants to resist a devastating blight disease has been identified by a multi-national team...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Euro Bio-inspired - International Conference and Exhibition on Bio-inspired Materials

23.07.2015 | Event News

Clash of Realities – International Conference on the Art, Technology and Theory of Digital Games

10.07.2015 | Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

 
Latest News

“Seeing” molecular interactions could give boost to organic electronics

03.08.2015 | Materials Sciences

Stroke: news about platelets

03.08.2015 | Life Sciences

Molecular Spies to Fight Cancer - Procedure for improving tumor diagnosis successfully tested

03.08.2015 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>