To sort out the differences between these results, the authors isolated the DNA itself from the mouse brains. This confirmed that breaks in the DNA were more common in animals that have been put in an enriched environment. As many as 40 percent of their cells had DNA that showed signs of damage.
Much of the rest of the paper is focused on figuring out what’s going on. The authors tested whether neural activity alone was sufficient to cause this by shining light into the animal’s eye while they were anesthetized; that worked too. So did activating neural activity in the brain itself. So, it’s pretty clear that the double strand breaks were an outcome of neural activity. By using various inhibitors, the researchers even narrowed it down to a single neural signaling molecule, called glutamate.
The obvious question here is why nerve cells end up picking up DNA damage when doing what is, effectively, their job. One hypothesis is that the nerve cells can’t help it. Nerve activity is inherently energy-intensive, and high metabolic activity tends to create oxygen radicals that can damage DNA. But treatment with antioxidants didn’t stop the breaks from occurring, which seems to suggest we need to look elsewhere for an explanation. The authors suggest it may be a consequence of the changes in gene activity that follow nerve firing.
Could this result in long-term damage? As far as the researchers could tell, the breaks were repaired within a day, which suggests that any problems should be transient. And a number of other studies have shown that remaining mentally active helps protect you from the common forms of mental decline that occur with old age. So, all of that argues this isn’t something to keep you up at night. Nevertheless, the authors suggest that the additional damage associated with a disease state—in their case, Alzheimer’s—could overwhelm the repair system and contribute to the disease’s progression.
Nature Neuroscience, 2013. DOI: 10.1038/nn.3356 (About DOIs).