Featured Research

from universities, journals, and other organizations

Gene silencing spurs fountain of youth in mouse brain

Date:
February 7, 2013
Source:
Helmholtz Association of German Research Centres
Summary:
Cognitive decline in old age is linked to decreasing production of new neurons. Scientists have discovered in mice that significantly more neurons are generated in the brains of older animals if a signaling molecule called Dickkopf-1 is turned off. In tests for spatial orientation and memory, mice in advanced adult age whose Dickkopf gene had been silenced reached an equal mental performance as young animals.

Newborn neurons (in green) in the brain of a 3 month old mouse.
Credit: German Cancer Research Center

Cognitive decline in old age is linked to decreasing production of new neurons. Scientists from the German Cancer Research Center have discovered in mice that significantly more neurons are generated in the brains of older animals if a signaling molecule called Dickkopf-1 is turned off. In tests for spatial orientation and memory, mice in advanced adult age whose Dickkopf gene had been silenced reached an equal mental performance as young animals.

The hippocampus -- a structure of the brain whose shape resembles that of a seahorse -- is also called the "gateway" to memory. This is where information is stored and retrieved. Its performance relies on new neurons being continually formed in the hippocampus over the entire lifetime. "However, in old age, production of new neurons dramatically decreases. This is considered to be among the causes of declining memory and learning ability," Prof. Dr. Ana Martin-Villalba, a neuroscientist, explains.

Martin-Villalba, who heads a research department at the German Cancer Research Center (DKFZ), and her team are trying to find the molecular causes for this decrease in new neuron production (neurogenesis). Neural stem cells in the hippocampus are responsible for continuous supply of new neurons. Specific molecules in the immediate environment of these stem cells determine their fate: They may remain dormant, renew themselves, or differentiate into one of two types of specialized brain cells, astrocytes or neurons. One of these factors is the Wnt signaling molecule, which promotes the formation of young neurons. However, its molecular counterpart, called Dickkopf-1, can prevent this.

"We find considerably more Dickkopf-1 protein in the brains of older mice than in those of young animals. We therefore suspected this signaling molecule to be responsible for the fact that hardly any young neurons are generated any more in old age." The scientists tested their assumption in mice whose Dickkopf-1 gene is permanently silenced. Professor Christof Niehrs had developed these animals at DKFZ. The term "Dickkopf" (from German "dick" = thick, "Kopf" = head) also goes back to Niehrs, who had found in 1998 that this signaling molecule regulates head development during embryogenesis.

Martin-Villalba's team discovered that stem cells in the hippocampus of Dickkopf knockout mice renew themselves more often and generate significantly more young neurons. The difference was particularly obvious in two-year old mice: In the knockout mice of this age, the researchers counted 80 percent more young neurons than in control animals of the same age. Moreover, the newly formed cells in the adult Dickkopf-1 mutant mice matured into potent neurons with multiple branches. In contrast, neurons in control animals of the same age were found to be more rudimentary already.

Blocking Dickkopf improves spatial orientation and memory

Several years ago, Ana Martin-Villalba had shown that mice lose their spatial orientation when neurogenesis in the hippocampus is blocked. Now, is it possible that the young neurons in Dickkopf-deficient mice improve the animals' cognitive performance? The DKFZ researchers used standardized tests to study how the mice orient themselves in a maze. While in the control animals, the younger ones (3 months) performed much better in orienting themselves than the older ones (18 months), the Dickkopf-1-deficient mice showed no age-related decline in spatial orientation capabilities. Older Dickkopf-1 mutant mice also outperformed normal animals in tests determining spatial memory.

"Our result proves that Dickkopf-1 promotes age-related decline of specific cognitive abilities," says Ana Martin-Villalba. "Although we had expected silencing of Dickkopf-1 to improve spatial orientation and memory of adult mice, we were surprised and impressed that animals in advanced adult age actually reach the performance levels of young animals."

These results give rise to the question whether the function of Dickkopf-1 may be turned off using drugs. Antibodies blocking the Dickkopf protein are already being tested in clinical trials for treating a completely different condition. "It is fascinating to speculate that such a substance may also slow down age-related cognitive decline. But this is still a dream of the future, since we have only just started first experiments in mice to explore this question."


Story Source:

The above story is based on materials provided by Helmholtz Association of German Research Centres. Note: Materials may be edited for content and length.


Journal Reference:

  1. Dιsirιe R.M. Seib, Nina S. Corsini, Kristina Ellwanger, Christian Plaas, Alvaro Mateos, Claudia Pitzer, Christof Niehrs, Tansu Celikel, Ana Martin-Villalba. Loss of Dickkopf-1 Restores Neurogenesis in Old Age and Counteracts Cognitive Decline. Cell Stem Cell, 2013; 12 (2): 204 DOI: 10.1016/j.stem.2012.11.010

Cite This Page:

Helmholtz Association of German Research Centres. "Gene silencing spurs fountain of youth in mouse brain." ScienceDaily. ScienceDaily, 7 February 2013. <www.sciencedaily.com/releases/2013/02/130207150911.htm>.
Helmholtz Association of German Research Centres. (2013, February 7). Gene silencing spurs fountain of youth in mouse brain. ScienceDaily. Retrieved September 15, 2014 from www.sciencedaily.com/releases/2013/02/130207150911.htm
Helmholtz Association of German Research Centres. "Gene silencing spurs fountain of youth in mouse brain." ScienceDaily. www.sciencedaily.com/releases/2013/02/130207150911.htm (accessed September 15, 2014).

Share This



More Health & Medicine News

Monday, September 15, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Respiratory Virus Spreads To Northeast, Now In 21 States

Respiratory Virus Spreads To Northeast, Now In 21 States

Newsy (Sep. 14, 2014) — The respiratory virus Enterovirus D68, which targets children, has spread from the Midwest to 21 states. Video provided by Newsy
Powered by NewsLook.com
Shocker: Journalists Are Utterly Addicted To Coffee

Shocker: Journalists Are Utterly Addicted To Coffee

Newsy (Sep. 13, 2014) — A U.K. survey found that journalists consumed the most amount of coffee, but that's only the tip of the coffee-related statistics iceberg. Video provided by Newsy
Powered by NewsLook.com
Contagious Respiratory Illness Continues to Spread Across U.S.

Contagious Respiratory Illness Continues to Spread Across U.S.

Reuters - US Online Video (Sep. 12, 2014) — Hundreds of children in several states have been stricken by a serious respiratory illness that is spreading across the U.S. Linda So reports. Video provided by Reuters
Powered by NewsLook.com
Ebola Batters Sierra Leone Economy Too

Ebola Batters Sierra Leone Economy Too

Reuters - Business Video Online (Sep. 12, 2014) — The World Health Organisation warns that local health workers in West Africa can't keep up with Ebola - and among those countries hardest hit by the outbreak, the economic damage is coming into focus, too. As David Pollard reports, Sierra Leone admits that growth in one of the poorest economies in the region is taking a beating. Video provided by Reuters
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:

More Coverage


Potential Target for Age-Related Cognitive Decline Identified

Feb. 7, 2013 — As the elderly age, their ability to concentrate, reason, and recall facts tends to decline in part because their brains generate fewer new neurons than they did when they were younger. Now, ... read more
from the past week

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