A new study published in Cell Stem Cell by scientists from the University of Southern California (USC) explores the link between traumatic brain injury (TBI) and the increased risk of developing neurodegenerative diseases such as ALS and dementia. Using lab-grown human brain structures called organoids, the researchers were able to mimic the effects of TBI and study its impact on nerve cells. The study, led by former postdoc Jesse Lai and PhD student Joshua Berlind, showed that injured organoids displayed nerve cell death and pathological changes in proteins associated with TBI.
The researchers found that these pathological changes were more prevalent in organoids derived from patients with ALS or frontotemporal dementia, indicating a genetic predisposition that could increase the risk of developing these conditions following a TBI. The most severe injuries were observed in excitatory neurons located in the deep layers of the organoids, suggesting a vulnerable population of nerve cells that are at higher risk of dysfunction and death post-injury. To address this, the scientists identified a gene called KCNJ2, which plays a role in potassium channel regulation, as a potential target for protecting nerve cells against the effects of TBI.
Inhibiting the KCNJ2 gene had a protective effect on organoids derived from both ALS patients and non-ALS patients, as well as on mice following a TBI. This approach could potentially be used as a post-injury treatment or a preventive measure for individuals at high risk of TBI, such as athletes. Co-corresponding author Justin Ichida, an expert in stem cell biology and regenerative medicine at USC, highlighted the potential of targeting the KCNJ2 gene to reduce nerve cell death after TBI and mitigate the associated risks of developing neurodegenerative diseases.
The study’s authors, including PhD student Joshua Berlind and co-author Violeta Yu, bring a wealth of experience and expertise in stem cell research and neurology to the project. The research was supported by federal funding from the National Institute of Neurological Disorders and Stroke (NINDS) and the National Institute on Aging, as well as private funding from organizations such as Amgen, the New York Stem Cell Foundation, and the Alzheimer’s Drug Discovery Foundation. The study’s findings shed light on the mechanisms underlying the link between TBI and neurodegenerative diseases and offer potential therapeutic targets to protect nerve cells in individuals at risk of TBI-induced conditions.
The researchers’ use of organoids derived from patient stem cells provides a valuable tool for studying the effects of TBI on nerve cells and investigating potential treatments to mitigate these effects. By identifying the role of the KCNJ2 gene in protecting nerve cells post-injury, the study offers new insights into the mechanisms underlying TBI-related neurodegeneration and provides a potential avenue for developing targeted therapies. The study’s findings underscore the importance of understanding the impact of TBI on the brain and the potential for identifying personalized treatments to reduce the risk of developing neurodegenerative diseases following a traumatic brain injury.
