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Dickkopf molecule makes fountain of youth in the brain run dry, say researchers

Researchers have found the cause of age-related cognitive decline.

Age-related cognitive decline is associated with decreasing production of new neurons. Researchers from the German Cancer Research Center have discovered that significantly more neurons are generated in the brains of older animals if a signaling molecule called Dickkopf-1 is turned off, according to a news release from the Helmholtz Association of German Research Centres.

In tests for spatial orientation and memory, older mice whose Dickkopf gene had been turned off achieved an equal mental performance as young mice.

The hippocampus’ performance relies on new neurons being continually formed over a person’s 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,” says neuroscientist¬†Ana Martin-Villalba.

Martin-Villalba and her research team at the German Cancer Research Center are trying identify the molecular causes for this decrease in new neuron production. Neural stem cells in the hippocampus are responsible for supplying the brain with new neurons. However, specific molecules in the immediate environment of these stem cells decide the fate of the new neurons. For example, the Dickkopf-1 molecule can prevent the formation of young neurons.

“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,” write the authors.

The researchers tested their theory in mice whose Dickkopf-1 gene is permanently silenced.

Martin-Villalba and her research team found that stem cells in the hippocampus of these mice renew themselves more often and generate significantly more neurons. Two-year old versions of these mice had 80 percent more young neurons than control animals of the same age. They report that the newly formed cells in the these mice matured into potent neurons with multiple branches.

Researchers also determined that Dickkopf-deficient mice have better spatial orientation and memory than the control animals. They used standardized tests to examine how the mice orient themselves in a maze. The Dickkopf-1-deficient mice revealed no age-related decline in spatial orientation or memory capabilities.

“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.”

Researchers are looking into whether Dickkopf-blocking drugs could slow down age-related cognitive decline.