Stress-Induced Chromosome Changes Protect Flies’ Aging Brains

ABOVE: When exposed to oxidative stress, Drosophila brain cells (glia shown above) can develop more than two sets of chromosomes—a state that may protect the brain from damage.
NANDAKUMAR ET AL., 2020

EDITOR’S CHOICE IN CELL BIOLOGY

The paper
S. Nandakumar et al., “Polyploidy in the adult Drosophila brain,” eLife, 9:e54385, 2020.

Over a lifetime, mature brain cells face a gauntlet of oxidative stress, DNA damage, and other dangers that can lead to neurodegeneration. In response, Drosophila’s brain cells acquire additional sets of chromosomes beyond the normal two. These chromosome-packed cells appear to be more resistant to cell death, suggesting polyploidy plays a protective role in the fly brain, University of Michigan molecular cell biologist Shyama Nandakumar and colleagues found.

Although the researchers knew that cell damage can lead to the accumulation of additional sets of chromosomes in some cases, such as in the human liver and in the brains of patients with Alzheimer’s disease, not much was known about the mechanism behind it or what its function could be. 

To study polyploidy, Nandakumar and the rest of the team in Laura Buttitta’s lab used a brain dissection technique developed by teammate Olga Grushko, along with highly sensitive flow cytometry. When aging fly brains were exposed to oxidative stress, cells in certain areas such as the optic lobes were more likely to obtain extra chromosome sets than cells in other spots. The cells acquired the extra sets after reverting back into the cell cycle. And notably, as the number of polyploid cells in an area grew, the rate of local cell death declined.

The findings came as a surprise, Nandakumar notes. “It took us a while to convince ourselves that what we were observing was actually true.”

The study “fits with the emerging theme that polyploidy emerges as a response to tissue stress,” Donald Fox, a genomicist at Duke University Medical Center who was not involved with the research, writes in an email to The Scientist. “And the fact that these polyploid cells are in the brain raises really interesting questions about the role of polyploidy in aged/stressed neural circuits, and how this might impact behavior.”