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Researchers identify potential target for age-related cognitive decline

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, researchers reporting in the February 7th issue of the Cell Press journal Cell Stem Cell have discovered a molecule that accumulates with age and inhibits the formation of new neurons. The finding might help scientists design therapies to prevent age-related cognitive decline.

The investigators identified the molecule, called Dickkopf-1 or Dkk1, in the brains of aged mice. By blocking production of Dkk1, "We released a brake on neuronal birth, thereby resetting performance in spatial memory tasks back to levels observed in younger animals," says senior author Dr. Ana Martin-Villalba, of the German Cancer Research Center in Heidelberg.

Aged mice that lacked Dkk1 performed just as well as young mice in memory and recognition tests because the ability of the neural stem cells in their brains to self-renew and generate immature neurons was restored to youthful levels.

The investigators also found that young mice lacking Dkk1 were less susceptible to developing acute stress-induced depression than normal mice. This suggests that, in addition to slowing memory loss during aging, neutralizing Dkk1 (which is also present in human brains) could be beneficial in counteracting symptoms of depression.

Dr. Martin-Villalba notes that there are ongoing clinical trials of biological inhibitors of Dkk1 for other medical purposes. "The design of inhibitors that reach the brain might enable the prevention of cognitive decline in the aging population and depression in the general population," she says.

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