Scientists have discovered that a certain type of DNA damage associated with Alzheimer's disease can also be an integral part of normal brain functions such as learning.
A particular type of deoxyribonucleic acid (DNA) damage, known as a double-strand break, or DSB, has long been considered a major force behind age-related illnesses such as Alzheimer's.
Researchers at the Gladstone Institutes in the US found that DSBs in neuronal cells in the brain can also be part of normal brain functions such as learning - as long as the DSBs are tightly controlled and repaired in good time.
Further, the accumulation of the amyloid-beta protein in the brain - widely thought to be a major cause of Alzheimer's disease - increases the number of neurons with DSBs and delays their repair.
In laboratory experiments, two groups of mice explored a new environment filled with unfamiliar sights, smells and textures. One group was genetically modified to simulate key aspects of Alzheimer's, and the other was a healthy, control group.
As the mice explored, their neurons became stimulated as they processed new information. After two hours, the mice were returned to their familiar, home environment.
The investigators then examined the neurons of the mice for markers of DSBs. The control group showed an increase in DSBs right after they explored the new environment - but after being returned to their home environment, DSB levels dropped.
"We were initially surprised to find neuronal DSBs in the brains of healthy mice," said Elsa Suberbielle, the paper's lead author.
"But the close link between neuronal stimulation and DSBs, and the finding that these DSBs were repaired after the mice returned to their home environment, suggest that DSBs are an integral part of normal brain activity.
"We think that this damage-and-repair pattern might help the animals learn by facilitating rapid changes in the conversion of neuronal DNA into proteins that are involved in forming memories," Suberbielle said.
The group of mice modified to simulate Alzheimer's had higher DSB levels at the start - levels that rose even higher during neuronal stimulation. In addition, the team noticed a substantial delay in the DNA-repair process.
