Researchers identify potential target for age-related cognitive decline
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."
More information: Seib et al.: "Loss of Dickkopf-1 restores neurogenesis in old age and counteracts cognitive decline." dx.doi.org/10.1016… .2012.11.010
Journal reference: Cell Stem Cell
Provided by Helmholtz Association of German Research Centres
- Scientists discover that specific antibodies halt Alzheimer's disease in mice Mar 06, 2012 | not rated yet | 0
- Memory formation triggered by stem cell development Feb 23, 2012 | not rated yet | 0
- Researchers show how memory is lost -- and found Jul 27, 2011 | not rated yet | 0
- Study shows neural stem cells in mice affected by gene associated with longevity Nov 05, 2009 | not rated yet | 0
- Researchers find a link between age related memory loss and a specific enzyme in mice Jul 02, 2012 | not rated yet | 0
- Motion perception revisited: High Phi effect challenges established motion perception assumptions Apr 23, 2013 | 3 / 5 (2) | 2
- Anything you can do I can do better: Neuromolecular foundations of the superiority illusion (Update) Apr 02, 2013 | 4.5 / 5 (11) | 5
- The visual system as economist: Neural resource allocation in visual adaptation Mar 30, 2013 | 5 / 5 (2) | 9
- Separate lives: Neuronal and organismal lifespans decoupled Mar 27, 2013 | 4.9 / 5 (8) | 0
- Sizing things up: The evolutionary neurobiology of scale invariance Feb 28, 2013 | 4.8 / 5 (10) | 14
How can there be villous adenoma in colon, if there are no villi there
4 hours ago As title suggest. Thanks :smile:
How can there be a term called "intestinal metaplasia" of stomach
May 21, 2013 Hello everyone, Ok Stomach's normal epithelium is simple columnar, now in intestinal type of adenocarcinoma of stomach it undergoes "intestinal...
Pressure-volume curve: Elastic Recoil Pressure don't make sense
May 18, 2013 From pressure-volume curve of the lung and chest wall (attached photo), I don't understand why would the elastic recoil pressure of the lung is...
If you became brain-dead, would you want them to pull the plug?
May 17, 2013 I'd want the rest of me to stay alive. Sure it's a lousy way to live but it beats being all-the-way dead. Maybe if I make it 20 years they'll...
MRI bill question
May 15, 2013 Dear PFers, The hospital gave us a $12k bill for one MRI (head with contrast). The people I talked to at the hospital tell me that they do not...
Ratio of Hydrogen of Oxygen in Dessicated Animal Protein
May 13, 2013 As an experiment, for the past few months I've been consuming at least one portion of Jell-O or unflavored Knox gelatin per day. I'm 64, in very...
- More from Physics Forums - Medical Sciences
More news stories
On May 22, JoVE will publish details of a technique to measure the health of human genetic material in relation to a patient's age. The method is demonstrated by the laboratory of Dr. Gil Atzmon at New York's Albert Einste ...
Medical research 2 hours ago | not rated yet | 0
(Medical Xpress)—Scientists supported by the National Institutes of Health have a new theory as to why a woman's fertility declines after her mid-30s. They also suggest an approach that might help slow ...
Medical research 3 hours ago | not rated yet | 0 |
Medical researchers discover new ways to target, develop and design drugs to prevent and treat viral infection
Researchers at the University of Alberta have discovered a new drug target, developed a new drug and identified a new way to design drugs—all of which could be a winning combination in the battle against viruses.
Medical research 4 hours ago | 4 / 5 (1) | 0 |
New research at The University of Nottingham aimed at preventing harmful blood clots associated with heart disease and stroke has recently received a major funding boost from the British Heart Foundation.
Medical research 4 hours ago | not rated yet | 0
Italian lawmakers on Wednesday gave their final approval to a law that allows limited use of a controversial type of stem cell therapy which has been condemned by many scientists but has given hope to families of terminally-ill ...
Medical research 4 hours ago | 5 / 5 (1) | 1
Researchers at Johns Hopkins have unraveled the molecular foundations of cocaine's effects on the brain, and identified a compound that blocks cravings for the drug in cocaine-addicted mice. The compound, already proven safe ...
6 minutes ago | not rated yet | 0 |
Scientists have reversed behavioral and brain abnormalities in adult mice that resemble some features of schizophrenia by restoring normal expression to a suspect gene that is over-expressed in humans with ...
6 minutes ago | not rated yet | 0 |
Costs to treat stroke are projected to more than double and the number of people having strokes may increase 20 percent by 2030, according to the American Heart Association/American Stroke Association.
6 minutes ago | not rated yet | 0
University of Granada scientists have patented a new treatment for acne that is based on completely natural substances and is much more effective than artificial formulas because it does not create resistance ...
13 minutes ago | not rated yet | 0
The new 13-valent pneumococcal conjugate vaccine (PCV13) appears to be as safe as the previous version used prior to 2010, the 7-valent pneumococcal conjugate vaccine (PCV7), according to a Kaiser Permanente study published ...
1 hour ago | not rated yet | 0
Is it permissible to harm one to save many? Those who tend to say "yes" when faced with this classic dilemma are likely to be deficient in a specific kind of empathy, according to a report published in the scientific journal ...
7 hours ago | not rated yet | 0 |