Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Scientists Discover DNA Damage Occurs as Part of Normal Brain Activity

Published: Thursday, April 04, 2013
Last Updated: Thursday, April 04, 2013
Bookmark and Share
Findings at Gladstone Institutes support strategies to fight Alzheimer’s disease.

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.

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.

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 (Aβ) 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, according to Mucke, who directs neurological research at Gladstone and is a professor of neuroscience and neurology at UC San Francisco, with which Gladstone is affiliated.

“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.”

DSBs Found in Healthy Brains

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.

Restoring Neuronal Communication

To counteract the accumulation of DSBs, the team first used a therapeutic approach built on two recent studies – one of which was led by 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,” Mucke said. “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.


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 4,000+ scientific posters on ePosters
  • More than 5,300+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Scientists Create Heart Cells Better, Faster, Stronger
Scientists at Gladstone Institutes have pinpointed two chemicals that help the heart convert scar tissue into healthy cardiac muscle.
Friday, November 18, 2016
Enhancing Scar Tissue Repair
Scientists identify chemicals that improve the ability of cells to transition from scar tissue to healthy tissues.
Tuesday, November 15, 2016
Genetic Disease Research Reveals New Stem Cell Pathway
Scientists enhance efficiency of stem cell reprogramming with gene mutation that causes “stone man syndrome”.
Tuesday, November 01, 2016
Ancient Anti-Inflammatory Drug Has Cancer-Fighting Properties
Eric Verdin, MD, Gladstone Institutes, has made a new discovery about an ancient drug that could lead to alternative treatments for cancer and inflammatory diseases.
Wednesday, June 01, 2016
Scientists Discover that DNA Damage Occurs as Part of Normal Brain Activity
Findings provide additional support for strategies to fight Alzheimer’s disease.
Tuesday, March 26, 2013
Gladstone, Stanford Scientists Collaborate to Block Lou Gehrig’s Disease Protein
Findings suggest therapeutic target for treating devastating and fatal disease.
Thursday, November 01, 2012
Gladstone Scientists Offer New Insight into the Regulation of Stem Cells and Cancer Cells
Breakthrough discovery is likely to advance medicine and human health.
Tuesday, August 23, 2011
Scientific News
Big Genetics in BC: The American Society for Human Genetics 2016 Meeting
Themes at this year's meeting ranged from the verification, validation, and sharing of data, to the translation of laboratory findings into actionable clinical results.
Personality Traits, Psychiatric Disorders Linked to Specific Genomic Locations
Researchers have unearthed genetic correlations between personality traits and psychiatric disorders.
Genetics Control Regenerative Properties Of Stem Cells
Researchers define how genetic factors control regenerative properties of blood-forming stem cells.
Diabetes Missing Link Discovered
Researchers from the University of Auckland have shown that beta catenin plays a vital role in the control of insulin release from the pancreas.
Study Reveals New Role for Hippo Pathway in Suppressing Cancer Immunity
Hippo pathway signaling regulates organ size by moderating cell growth, apoptosis and stem cell renewal, but dysregulation contributes to cancer development.
Gene-Editing Improves Vision in Blind Rats
Scientists developed a targeted gene-replacement technique that can modify genes in both dividing and non-dividing cells in living animals.
Gene Editing Yields Tomatoes That Ripen Weeks Earlier
Research team develop method to make tomato plants flower and ripen fruit two weeks faster than current growth rates.
Exploring the Genome of the River Blindness Parasite
Researchers have decoded the genome of the parasite that causes the skin and eye infection known as river blindness.
Gene Therapy Maintains Clotting Factor for Hemophilia Patients
Following a single gene therapy dose, the highest levels of an essential blood clotting factor IX were observed in hemophilia B patients.
Unexpected Role for Epigenetic Enzymes in Cancer
Researchers use epigenetics to identify the role of an enzyme family as regulators of genetic message interpretation in yeast.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
4,000+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,300+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!