Navigation Links
A new approach to Huntington's disease?
Date:3/30/2014

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' excitabilityor 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.


'/>"/>
Contact: Elaine Schmidt
eschmidt@mednet.ucla.edu
310-794-2272
University of California - Los Angeles Health Sciences
Source:Eurekalert

Related biology news :

1. Stanford scientists develop gene therapy approach to grow blood vessels in ischemic limbs
2. A project to research biological and chemical aspects of microalgae to fuel approach
3. UofL research holds promise of therapeutic approach for gum disease
4. Approach to diabetes self-management too narrow, study suggests
5. Manatee hearing good enough to sense approaching motorboats
6. Scripps Florida scientist awarded $1.5 million to design therapeutics with new RNA approach
7. New approach to spell checking gene sequences
8. Powerful new approach to attack flu virus
9. Potential new approach to regenerating skeletal muscle tissue
10. Bugs have key role in farming approach to storing CO2 emissions
11. Computing advances vital to sustainability efforts; new report recommends problem-focused, iterative approach to research
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:1/25/2017)... NEW YORK , Jan. 25, 2017 /PRNewswire/ ... and Access Management (IAM) lifecycle is comprised of ... infrastructure for the purpose of maintaining digital identities ... enterprise resources and applications. There are significant number ... compliance from time to time by optimizing processes ...
(Date:1/19/2017)... , January 19, 2017 According to a new ... and Forecast, 2014 - 2022," the global biometric sensor market is expected to ... to 2022. In 2015, Asia-Pacific dominated the global market ... private sectors. Continue Reading ... ...
(Date:1/12/2017)... , Jan. 12, 2017  Trovagene, Inc. (NASDAQ: ... DNA (ctDNA) technologies, today announced that it has signed ... and the Middle East ...  This milestone marks the first wave of international distribution ... urine and blood samples. The initial partners ...
Breaking Biology News(10 mins):
(Date:2/16/2017)... -- Research and Markets has announced the ... report to their offering. ... The study scope ... plasmids, chassis organisms, synthetic cells, production systems), enabling technologies ... and specialty media) and enabled technologies (biofuels, chemicals, pharmaceuticals, ...
(Date:2/16/2017)... HOLLISTON, Mass. , Feb. 16, 2017   ... or the "Company"), a biotechnology company developing bioengineered organ ... the esophagus, bronchus and trachea, announced today the closing ... offering of 20,000,000 shares of common stock and warrants ... gross proceeds of $8.0 million. The offering was priced ...
(Date:2/16/2017)... , Feb. 16, 2017 UCHealth ( ... to utilize LungDirect for pulmonary nodule patient management. In ... nodule, or a spot on the lung, UCHealth looks ... on manual data entry. Stephanie Brown, ... tracking my nodule patients with an Excel spreadsheet, which ...
(Date:2/16/2017)... HACKENSACK, N.J. , Feb. 16, 2017  Champions ... engaged in the development and sale of advanced technology ... of oncology drugs, today announced the addition of new ... These new models will expand Champions, product ... cancer, head and neck cancer, AML, and non-small cell ...
Breaking Biology Technology: