Breaking in Order to Build

Image courtesy of the Journal of Cell Biology
Image of labeled (red) DNA breaks in a single cell courtesy of the Journal of Cell Biology

Do you ever think about how every time you encounter something new your brain adjusts and rewires and makes molecular changes so you can remember this new object in the context of what you already know? I know I do, though that may be a by-product of my neuroscience upbringing. Even if you don’t think about it, it’s happening. Complex changes in the numbers and amounts of gene expression are critical to developing and maintaining memories. And as it turns out, breaking the DNA in your brain cells into pieces is also part of the process.

Seems a bit counter-productive right? Even downright dangerous? Cancer is caused by random DNA damage in other kinds of cells. New work in Nature Neuroscience shows that some level of DNA breakage (Double-Strand Breaks, DSB) in neurons accompanies the exposure of an animal to a new environment. As the animal explores its new environment and learns the layout of the enclosure, new memories are being generated and DSBs are observed at a high level in the dentate gyrus, known to be involved in learning and memory. These breaks can be observed throughout the brain at a low level, but they are increased in frequency in the part of the brain devoted to learning and memory. This result is highly unexpected so the group performing the study confirmed their results with several different assays that activate neurons. They provided visual stimulus to immobilized mice and they specifically activated regions of the brain with light activated ion channels. Each of these methods caused DSBs in DNA in response. These breaks seem to be repaired within 24 hours of the exposure to a new environment, suggesting the normal DNA repair machinery is acting efficiently and that these breaks are truly associated with the exposure stimulus.

As we age, both normally, and when affected by neurodegenerative diseases the number of these breaks tends to increase. Mouse models of Alzheimer’s disease have higher numbers of DNA breaks earlier in their lifetime. Eventually, this burden of repairing DNA can overwhelm the neurons and the cells can begin to malfunction. It’s really intriguing that activities like reading and doing crossword puzzles which are thought to be protective in cases of dementia, would also cause these DSBs, which seem to be related to disease progression. So   more breaks are good? Or are more breaks bad? If we can figure out the role these breaks play in healthy neurons, it could help us understand how to lessen the burden in cases of Alzheimer’s. It’s also possible that these breaks are related to the cellular stress of a large influx of calcium each time the neurons are activated and don’t actually contribute to learning and memory directly. Either way, it’s fascinating to speculate about why breaking neuronal DNA into pieces is happening all the time.

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