Neuron Cell Death Helps Maintain Brain Balance: Study

A type of cell death linked to iron and oxidative stress could be playing a role in keeping the brain healthy by helping maintain a balance while producing new neurons in the hippocampus, which is critical for memory and learning. "Ferroptosis (type of cell death) has been identified in almost every neurological disorder where cells are dying, including Alzheimer's disease, Parkinson's disease and stroke," Tara Walker, associate professor at the Queensland Brain Institute, The University of Queensland in Australia and author of the study published in the journal Cell Stem Cell, said. "But we wanted to know whether it also had a role in normal brain function," Walker said.

Researchers focused on neurogenesis in adult mice, or the process by which neural stem cells in the hippocampus divide, mature and can become new neurons. The newborn neurons help support learning and memory, but the process is known to slow down with age.

The study, which looked at neurons in the mice's hippocampus, found that ferroptosis was one way that neural stem cells were lost in the ageing brain.

Author Alison Carlisle, postdoctoral research fellow at The University of Queensland, explained that neurogenesis is decreased and a declining cognition are a part of ageing and that neural stem cells were especially vulnerable to ferroptosis-related stress.

"When compounds that block ferroptosis were given to aged mice, the animals produced more new neurons and performed better in spatial learning and memory tasks," Carlisle said.

In a previous study, Walker's team showed that selenium supplements could increase neuron production and improve cognition in elderly mice. Selenium is important because it helps regulate 'GPX4', a protein that protects cells from ferroptosis, Walker said.

"That gave us a clue. We knew selenium increased neurogenesis and cognition, but we didn't know the mechanism. Ferroptosis helped explain how selenium might be protecting these cells from dying," Walker added.

The findings suggest ferroptosis may not only be a destructive process in disease, but also part of the brain's normal system for maintaining balance.

"It's all about balance -- not simply to make the brain produce as many new neurons as possible. This is the first report of a physiological role for ferroptosis in maintaining that balance," Carlisle said.

"When the brain is already performing well, you don't necessarily want to increase neurogenesis. But when there's a deficit, such as in ageing, stroke or neurodegenerative disease, this pathway may give us a way to help restore function," she said.

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