Researchers at the University of Notre Dame found that chronic physical compression of brain tissue kills neurons by activating programmed cell-death signals. The loss of neurons is irreversible and can lead to sensory loss, motor impairment and cognitive decline.
The team, led by Meenal Datta and Christopher Patzke, grew networks of neurons and glial cells from induced pluripotent stem cells (iPSCs) and applied sustained pressure to mimic compression by a glioblastoma. Graduate students Maksym Zarodniuk and Anna Wenninger compared which cells survived and which died after compression.
By sequencing messenger RNA, the researchers found increased HIF-1 levels, which activate stress-response genes, and elevated AP-1 expression, a marker of neuroinflammation. Data from the Ivy Glioblastoma Atlas Project and live compression experiments on preclinical brain models showed similar stress patterns and synaptic dysfunction.
The study suggests that the identified signaling pathways could become targets for drugs to reduce neuronal death, and the approach may apply to other conditions that change brain mechanics, such as traumatic brain injury.
Difficult words
- compression — pressure applied to a body part or tissue
- neuron — nerve cell that sends and receives signalsneurons
- glial cell — support cell in the nervous systemglial cells
- glioblastoma — a fast-growing tumor that starts in brain
- irreversible — cannot be changed back to how it was
- neuroinflammation — inflammation and immune response inside the nervous system
- sequence — to find the order of genetic materialsequencing
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Discussion questions
- How might reducing neuronal death help people with brain tumours or traumatic brain injury?
- Do you think studying cell networks grown from iPSCs is a good model for human brain problems? Why or why not?
- What steps could researchers take next to turn these signaling pathways into drug treatments?
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