Scientists have identified a genetic switch that causes memory impairment in mice when it goes into ‘off’ mode, raising hopes of powerful new drugs to treat Alzheimer’s and other diseases.
As part of their research, Andre Fischer of the European Neuroscience Institute in Gottingen, 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.
The result was increased activity of a cluster of over 1500 genes, which are known to make proteins that are needed for the creation of new neurons -- a process that is necessary for learning in humans and mice, reports New Scientist.
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 find out what prevents elderly mice getting this genetic boost, the researchers 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. This acetyl ‘cap’ was missing in the older mice that had been set the same tasks. From this, the team concluded 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.
The study has been published in the journal Science.