Gene switch rejuvenates failing mouse brains

Gene switch rejuvenates failing mouse brains

Step aside, Sudoku. A genetic switch that causes memory impairment in ageing mice when it goes into "off" mode has been flicked on, restoring failing brains to a more youthful state.

If a similar switch can be found in people, it might provide a new way to keep ageing human brains young.
Cognitive decline, particularly memory impairment, is a normal part of ageing in humans and animals. Yet why this happens, and how we can prevent it, is largely unknown, says David Sweatt at the University of Alabama, Birmingham, who was not involved in the new work.

André Fischer of the European Neuroscience Institute in Göttingen, Germany, and colleagues forced 3-month-old mice to find their way around a new environment and assessed them on their ability to associate an electric shock with a particular environment.

New neurons
The result was increased activity of a cluster of over 1500 genes which are known make proteins that are needed for the creation of new neurons – a process that is necessary for learning in humans and mice.

This boost in gene expression did not occur in 16-month-old mice given the same tasks: the activity of their genes changed only slightly. The mice also did worse than the young ones at spatial learning and memory tasks.

To uncover what prevents elderly mice getting this genetic boost, Fischer analysed the DNA found in neurons in the hippocampus of both old and young mice.

They found that when young mice are learning, a molecular fragment known as an acetyl group binds to a particular point on the histone protein that DNA wraps itself around – with the result that the cluster of learning and memory genes on the surrounding DNA ends up close to the acetyl group.

DNA 'on' switch
This acetyl "cap" was missing in the older mice that had been set the same tasks. From this, the team concludes that the cap acts as an "on" switch for the cluster of learning and memory genes: removing the cap switches off the genes.

Next, by injecting an enzyme known to encourage caps to bind to any kind of histone molecule, Fischer's team artificially flipped the switch to the on position in old mice. The acetyl group returned to the histone molecule and the mice's learning and memory performance became similar to that of 3-month-old mice.

Fungi Can Quickly Mutate to Produce an Infectious Ability

Fungi have significant potential for "horizontal" gene transfer, a new study has shown, similar to the mechanisms that allow bacteria to evolve so quickly, become resistant to antibiotics and cause other serious problems.

This discovery, to be published March 18 in the journal Nature, suggests that fungi have the capacity to rapidly change the make-up of their genomes and become infectious to plants and possibly animals, including humans.

They are not nearly as confined to the more gradual processes of conventional evolution as had been believed, scientists say. And this raises issues not only for crop agriculture but also human health, because fungi are much closer on the "evolutionary tree" to humans than bacteria, and consequently fungal diseases are much more difficult to treat.

The genetic mechanisms fungi use to do this are different than those often used by bacteria, but the end result can be fairly similar. The evolution of virulence in fungal strains that was once believed to be slow has now been shown to occur quickly, and may force a renewed perspective on how fungi can behave, change and transfer infectious abilities.

"Prior to this we've believed that fungi were generally confined to vertical gene transfer or conventional inheritance, a slower type of genetic change based on the interplay of DNA mutation, recombination and the effects of selection," said Michael Freitag, an assistant professor of biochemistry and biophysics at Oregon State University.

"But in this study we found fungi able to transfer an infectious capability to a different strain in a single generation," he said. "We've probably underestimated this phenomenon, and it indicates that fungal strains may become pathogenic faster than we used to think possible."