Featured Research

from universities, journals, and other organizations

Metabolic Disorder Underlies Huntington's Disease

Date:
October 20, 2006
Source:
Cell Press
Summary:
A metabolic disorder underlies the brain effects found in those with Huntington's disease, researchers report in an advance article publishing online Oct. 19, 2006. The article will appear in the November 2006 issue of the journal Cell Metabolism, published by Cell Press.

A metabolic disorder underlies the brain effects found in those with Huntington's disease, researchers report in an advance article publishing online October 19, 2006. The article will appear in the November 2006 issue of the journal Cell Metabolism, published by Cell Press.

Related Articles


Their new evidence ties a metabolic defect to the loss of neurons in the striatum, the brain's "movement control" region. That neurodegeneration leads to the uncontrollable "dance-like" movements characteristic of the fatal, genetic disorder.

The findings may help to explain other symptoms of the disease, including weight loss, and could point to new avenues for therapy, according to the researchers.

"Huntington's has been thought of primarily as a neurological disease," said Albert R. La Spada of the University of Washington, Seattle. "Our findings underscore the fact that the condition includes other, underrecognized aspects."

The findings in Huntington's disease further highlight the possibility that other neurological conditions might also have a strong metabolic component, La Spada added.

Huntington's is relentlessly progressive, the researchers said, as patients succumb to the disease 10 to 25 years after its onset. The disease is caused by a genetic defect in which a repetitive sequence of DNA in the "huntingtin" (htt) gene gets expanded to encode an abnormally elongated protein.

Although the mutant htt protein is widely present, only certain populations of neurons degenerate and only a subset of other cell types are affected, they said. And exactly how the htt protein causes disease has remained uncertain.

The researchers made their current discovery after stumbling onto evidence that mice with Huntington's disease suffer extremely low body temperatures that worsen as the disease progresses.

"These mice have been around for at least a decade," La Spada said. "They have been the subjects of dozens, if not hundreds, of studies, but no one had checked one of their most basic vital signs.

"When you do, you find that the mice have a dramatic abnormality in temperature--which is normally tightly regulated."

Early on, the animals' temperature registered one or two degrees below normal, La Spada said. As their condition worsened, body temperatures fell substantially, he added, sometimes below 30C. Like humans, the normal body temperature of mice is about 37C.

To trace the causes of the animals' hypothermia, the researchers first looked to the brain region that controls body temperature. The animals brains, however, appeared to register and respond to cold normally.

The problem, they found, lay instead in fat cells known as brown adipose tissue (BAT). In rodents, BAT is the primary tissue that controls body temperature. When the brain signals that the body is cold, the gene called PGC-1 increases production of a protein in BAT that leads the cellular powerhouses known as mitochondria to generate heat instead of energy.

In the BAT of hypothermic Huntington's mice, PGC-1 levels rose but failed to elicit the other events required to maintain normal body temperature, they found.

The link to mitochondria-regulating PGC-1 led the team back to the brain, and specifically to the striatum. That brain region is most affected in Huntington's disease and is particularly sensitive to mitochondrial dysfunction.

The researchers found that tissue taken from striatums of Huntington's disease patients and mice showed reduced activity of genes controlled by PGC-1. They further found reduced mitochondrial function in the brains of Huntington's mice.

The findings suggest a link between two theories to explain Huntington's disease, the researchers said.

The earlier finding that the striatum is particularly sensitive to mitochondrial dysfunction suggested that the cellular powerhouses might play a role in the disease. Other evidence suggested that mutant htt might interfere with "transcription factors" that control gene activity.

"PGC-1 transcription interference may provide a link between transcription dysregulation and mitochondrial dysfunction in Huntington's disease," the researchers said. "More importantly, our study underscores an emerging role for metabolic and mitochondrial abnormalities in neurodegenerative disease."

As metabolic function generally diminishes in older people, such a connection might explain why many neurodegenerative diseases--such as Lou Gehrig's, Alzheimer's, and Parkinson's diseases, for example--tend to emerge and worsen with age, La Spada said.

The researchers include Patrick Weydt, Victor V. Pineda, Anne E. Torrence, Randell T. Libby, Terrence F. Satterfield, Merle L. Gilbert, Gregory J. Morton, Theodor K. Bammler, Richard P. Beyer, Courtney N. Easley, Annette C. Smith, Serge Luquet, Ian R. Sweet, Michael W. Schwartz, and Albert R. La Spada of University of Washington in Seattle; Eduardo R. Lazarowski of University of North Carolina in Chapel Hill; Andrew D. Strand of Fred Hutchinson Cancer Research Center in Seattle; and Libin Cui and Dimitri Krainc of Massachusetts General Hospital and Harvard Medical School in Boston. This work was supported by funding from Hereditary Disease Foundation, High Q, and grants from the NIH (DK17047 and DK063986 to I.R.S.; NS050352 to D.K.). A.R.L. is the recipient of a Paul Beeson Physician Faculty Scholar in Aging Research award from the American Foundation for Aging Research (AFAR), and V.V.P. is a NIH Genetics of Aging postdoctoral fellow (AG00057).

Weydt et al.: "Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1 in Huntington's disease neurodegeneration." Publishing in Cell Metabolism, Volume 4, Issue 5, November 2006.


Story Source:

The above story is based on materials provided by Cell Press. Note: Materials may be edited for content and length.


Cite This Page:

Cell Press. "Metabolic Disorder Underlies Huntington's Disease." ScienceDaily. ScienceDaily, 20 October 2006. <www.sciencedaily.com/releases/2006/10/061019192752.htm>.
Cell Press. (2006, October 20). Metabolic Disorder Underlies Huntington's Disease. ScienceDaily. Retrieved November 23, 2014 from www.sciencedaily.com/releases/2006/10/061019192752.htm
Cell Press. "Metabolic Disorder Underlies Huntington's Disease." ScienceDaily. www.sciencedaily.com/releases/2006/10/061019192752.htm (accessed November 23, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Sunday, November 23, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Could Your Genes Be The Reason You're Single?

Could Your Genes Be The Reason You're Single?

Newsy (Nov. 21, 2014) Researchers in Beijing discovered a gene called 5-HTA1, and carriers are reportedly 20 percent more likely to be single. Video provided by Newsy
Powered by NewsLook.com
Milestone Birthdays Can Bring Existential Crisis, Study Says

Milestone Birthdays Can Bring Existential Crisis, Study Says

Newsy (Nov. 21, 2014) Researchers find that as people approach new decades in their lives they make bigger life decisions. Video provided by Newsy
Powered by NewsLook.com
You Don't Have To Be Alcohol Dependent To Need Treatment

You Don't Have To Be Alcohol Dependent To Need Treatment

Newsy (Nov. 21, 2014) A study by the Centers for Disease Control and Prevention found 9 out of 10 excessive drinkers in the country are not alcohol dependent. Video provided by Newsy
Powered by NewsLook.com
Your Complicated Job Might Keep Your Brain Young

Your Complicated Job Might Keep Your Brain Young

Newsy (Nov. 20, 2014) Researchers at the University of Edinburgh found the more complex your job is, the sharper your cognitive skills will likely be as you age. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins