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 Collagen nanofibrils in mammalian tissues get stronger with exercise
14.12.2018 | University of Illinois College of Engineering

nachricht New discoveries predict ability to forecast dementia from single molecule
12.12.2018 | UT Southwestern Medical Center

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: An energy-efficient way to stay warm: Sew high-tech heating patches to your clothes

Personal patches could reduce energy waste in buildings, Rutgers-led study says

What if, instead of turning up the thermostat, you could warm up with high-tech, flexible patches sewn into your clothes - while significantly reducing your...

Im Focus: Lethal combination: Drug cocktail turns off the juice to cancer cells

A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.

The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...

Im Focus: New Foldable Drone Flies through Narrow Holes in Rescue Missions

A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.

Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...

Im Focus: Topological material switched off and on for the first time

Key advance for future topological transistors

Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...

Im Focus: Researchers develop method to transfer entire 2D circuits to any smooth surface

What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.

Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

ICTM Conference 2019: Digitization emerges as an engineering trend for turbomachinery construction

12.12.2018 | Event News

New Plastics Economy Investor Forum - Meeting Point for Innovations

10.12.2018 | Event News

EGU 2019 meeting: Media registration now open

06.12.2018 | Event News

 
Latest News

In search of missing worlds, Hubble finds a fast evaporating exoplanet

14.12.2018 | Physics and Astronomy

Collagen nanofibrils in mammalian tissues get stronger with exercise

14.12.2018 | Health and Medicine

Protein involved in nematode stress response identified

14.12.2018 | Life Sciences

VideoLinks
Science & Research
Overview of more VideoLinks >>>