The stupid squirrel participates in the age-related decline of mental abilities
The decline of cognitive abilities in old age is associated with a decrease in the activity of synthesis of new neurons in the hippocampus – the region of the brain considered responsible for memory. Researchers at the German Cancer Research Center, working under the guidance of Professor Ana Martin-Villalba, have found that blocking the activity of the Dickkopf-1 signaling molecule in the brains of old mice significantly enhances the production of new nerve cells. When performing tasks for orientation in space and memorization, such animals were not inferior to young mice.
The main objective of the work carried out by the authors is to study the molecular causes of the decrease in neurogenesis activity in the aging hippocampus. Stem cells localized in this structure ensure the renewal of nerve cells of the brain throughout life. The fate of these cells is regulated by certain molecules contained in their microenvironment: they can be at rest, self-renew, or differentiate into one of two types of specialized brain cells: astrocytes or neurons. One of these regulatory factors is the Wnt signaling molecule, which stimulates the formation of new neurons. As it turned out, its activity can be neutralized by the activity of another signaling molecule – Dickkopf-1. This protein, which got its name from the German "dick" – fat and "Kopf" – head (actually the word "Dickkopf" translates as "stubborn, stupid, stupid" :), was discovered in 1998 and is known as a signaling molecule involved in the formation of the head during embryonic development.)
The authors found that the concentration of the Dickkopf-1 protein in the brains of old mice significantly exceeds its concentration in the brain tissue of young animals. Based on this observation, they suggested that it is this signaling molecule that may be responsible for the decrease in the rate of production of new neurons observed as the body ages. This assumption was tested by creating genetically modified animals that do not have a functional variant of the gene encoding the Dickkopf-1 protein.
Further experiments have shown that stem cells localized in the hippocampus of animals of this lineage self-renew significantly more often and produce much more new neurons than hippocampal stem cells of ordinary mice. This difference turned out to be most pronounced in 2-year-old animals, in whose brains 80% more young neurons were formed than in the brains of control group animals. Moreover, it turned out that the newly formed cells of mutant animals matured into neurons with a large number of processes, whereas the emerging neurons of control mice of the same age had a more rudimentary structure.
Standard tests for orientation in a maze using animals aged 3 and 18 months showed that, unlike ordinary animals, whose spatial orientation deteriorates significantly with age, it does not suffer at all in aging mice that do not have the functional Dickkopf-1 gene. Similar results were obtained when comparing the preservation of spatial memory of ordinary and genetically modified mice.
The obtained results raise the question of the possibility of blocking the activity of the Dickkopf-1 gene or protein with the help of pharmacological drugs. Antibodies against the Dickkopf-1 protein are already undergoing clinical trials as a means to treat a completely different condition. According to the authors, it is very tempting to assume that such a drug will slow down the age-related decline of cognitive abilities. However, today this idea is just a dream, since the experiments conducted on mice are only the first step towards studying this issue.
Article by Seib et al. Loss of Dickkopf-1 restores neurogenesis in old age and counteracts cognitive decline published in the journal Cell Stem Cell.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on EurekAlert materials:
Dickkopf makes fountain of youth in the brain run dry.
11.02.2013