Featured Research

from universities, journals, and other organizations

DNA damage occurs as part of normal brain activity, scientists discover

Date:
March 24, 2013
Source:
Gladstone Institutes
Summary:
Scientists have discovered that a certain type of DNA damage long thought to be particularly detrimental to brain cells can actually be part of a regular, non-harmful process. The team further found that disruptions to this process occur in mouse models of Alzheimer's disease -- and identified two therapeutic strategies that reduce these disruptions.

Neurons. Scientists have discovered that a certain type of DNA damage long thought to be particularly detrimental to brain cells can actually be part of a regular, non-harmful process.
Credit: Roberto Robuffo / Fotolia

Scientists at the Gladstone Institutes have discovered that a certain type of DNA damage long thought to be particularly detrimental to brain cells can actually be part of a regular, non-harmful process. The team further found that disruptions to this process occur in mouse models of Alzheimer's disease -- and identified two therapeutic strategies that reduce these disruptions.

Related Articles


Scientists have long known that DNA damage occurs in every cell, accumulating as we age. But a particular type of DNA damage, known as a double-strand break, or DSB, has long been considered a major force behind age-related illnesses such as Alzheimer's. Today, researchers in the laboratory of Gladstone Senior Investigator Lennart Mucke, MD, report in Nature Neuroscience that DSBs in neuronal cells in the brain can also be part of normal brain functions such as learning -- as long as the DSBs are tightly controlled and repaired in good time. Further, the accumulation of the amyloid-beta protein in the brain -- widely thought to be a major cause of Alzheimer's disease -- increases the number of neurons with DSBs and delays their repair.

"It is both novel and intriguing team's finding that the accumulation and repair of DSBs may be part of normal learning," said Fred H. Gage, PhD, of the Salk Institute who was not involved in this study. "Their discovery that the Alzheimer's-like mice exhibited higher baseline DSBs, which weren't repaired, increases these findings' relevance and provides new understanding of this deadly disease's underlying mechanisms."

In laboratory experiments, two groups of mice explored a new environment filled with unfamiliar sights, smells and textures. One group was genetically modified to simulate key aspects of Alzheimer's, and the other was a healthy, control group. As the mice explored, their neurons became stimulated as they processed new information. After two hours, the mice were returned to their familiar, home environment.

The investigators then examined the neurons of the mice for markers of DSBs. The control group showed an increase in DSBs right after they explored the new environment -- but after being returned to their home environment, DSB levels dropped.

"We were initially surprised to find neuronal DSBs in the brains of healthy mice," said Elsa Suberbielle, DVM, PhD, Gladstone postdoctoral fellow and the paper's lead author. "But the close link between neuronal stimulation and DSBs, and the finding that these DSBs were repaired after the mice returned to their home environment, suggest that DSBs are an integral part of normal brain activity. We think that this damage-and-repair pattern might help the animals learn by facilitating rapid changes in the conversion of neuronal DNA into proteins that are involved in forming memories."

The group of mice modified to simulate Alzheimer's had higher DSB levels at the start -- levels that rose even higher during neuronal stimulation. In addition, the team noticed a substantial delay in the DNA-repair process.

To counteract the accumulation of DSBs, the team first used a therapeutic approach built on two recent studies -- one of which was led by Dr. Mucke and his team -- that showed the widely used anti-epileptic drug levetiracetam could improve neuronal communication and memory in both mouse models of Alzheimer's and in humans in the disease's earliest stages. The mice they treated with the FDA-approved drug had fewer DSBs. In their second strategy, they genetically modified mice to lack the brain protein called tau -- another protein implicated in Alzheimer's. This manipulation, which they had previously found to prevent abnormal brain activity, also prevented the excessive accumulation of DSBs.

The team's findings suggest that restoring proper neuronal communication is important for staving off the effects of Alzheimer's -- perhaps by maintaining the delicate balance between DNA damage and repair.

"Currently, we have no effective treatments to slow, prevent or halt Alzheimer's, from which more than 5 million people suffer in the United States alone," said Dr. Mucke, who directs neurological research at Gladstone and is a professor of neuroscience and neurology at the University of California, San Francisco, with which Gladstone is affiliated. "The need to decipher the causes of Alzheimer's and to find better therapeutic solutions has never been more important -- or urgent. Our results suggest that readily available drugs could help protect neurons against some of the damages inflicted by this illness. In the future, we will further explore these therapeutic strategies. We also hope to gain a deeper understanding of the role that DSBs play in learning and memory -- and in the disruption of these important brain functions by Alzheimer's disease."

Other scientists who participated in this research at Gladstone include Pascal Sanchez, PhD, Alexxai Kravitz, PhD, Xin Wang, Kaitlyn Ho, Kirsten Eilertson, PhD, Nino Devidze, PhD, and Anatol Kreitzer, PhD. This research was supported by grants from the National Institutes of Health and the S.D. Bechtel, Jr. Foundation.


Story Source:

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


Journal Reference:

  1. Elsa Suberbielle, Pascal E Sanchez, Alexxai V Kravitz, Xin Wang, Kaitlyn Ho, Kirsten Eilertson, Nino Devidze, Anatol C Kreitzer, Lennart Mucke. Physiologic brain activity causes DNA double-strand breaks in neurons, with exacerbation by amyloid-β. Nature Neuroscience, 2013; DOI: 10.1038/nn.3356

Cite This Page:

Gladstone Institutes. "DNA damage occurs as part of normal brain activity, scientists discover." ScienceDaily. ScienceDaily, 24 March 2013. <www.sciencedaily.com/releases/2013/03/130324152259.htm>.
Gladstone Institutes. (2013, March 24). DNA damage occurs as part of normal brain activity, scientists discover. ScienceDaily. Retrieved December 19, 2014 from www.sciencedaily.com/releases/2013/03/130324152259.htm
Gladstone Institutes. "DNA damage occurs as part of normal brain activity, scientists discover." ScienceDaily. www.sciencedaily.com/releases/2013/03/130324152259.htm (accessed December 19, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Friday, December 19, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Best Tips to Curb Holiday Carbs

The Best Tips to Curb Holiday Carbs

Buzz60 (Dec. 19, 2014) It's hard to resist those delicious but fattening carbs we all crave during the winter months, but there are some ways to stay satisfied without consuming the extra calories. Vanessa Freeman (@VanessaFreeTV) has the details. Video provided by Buzz60
Powered by NewsLook.com
Sierra Leone Bikers Spread the Message to Fight Ebola

Sierra Leone Bikers Spread the Message to Fight Ebola

AFP (Dec. 19, 2014) More than 100 motorcyclists hit the road to spread awareness messages about Ebola. Nearly 7,000 people have now died from the virus, almost all of them in west Africa, according to the World Health Organization. Video provided by AFP
Powered by NewsLook.com
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
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