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Research using minibrains cultivated in the lab may shed light on why traumatic brain injuries (TBIs) such as concussions are associated with an increased risk of dementia.
A recent study, published in the journal Cell Stem Cell on Thursday (April 4), described an experiment where researchers exposed lab-grown models of the human brain, referred to as cerebral organoids, to high-intensity ultrasonic waves. These waves were meant to mimic the damage to brain cells caused by severe TBIs.
The findings of the study suggest a potential approach to mitigate the consequences of brain injuries, as reported by the study authors. Theoretically, this treatment could serve as a preventative method or a post-injury therapy. However, further extensive studies are necessary before implementing such a treatment in clinical settings.
The cerebral organoids utilized in the study resembled small clumps of brain cells, rather than exact scaled-down replicas of full-fledged human brains. Nonetheless, organoids capture certain aspects of human biology that are challenging to replicate in animal models like laboratory mice. These organoids can be developed to encompass specific types of cells from various brain regions, organized in layers akin to the structure in a human brain.
Related: Even mild concussions can ‘rewire’ the brain, possibly causing long-term symptoms
In this particular research, the scientists cultivated the organoids using cells obtained from healthy individuals, as well as individuals with amyotrophic lateral sclerosis (ALS) or frontotemporal dementia, both neurodegenerative diseases. Studies have shown that mutations in a gene called C9orf72 increase the risk of developing these diseases. In this scenario, all donors carried a mutated copy of this gene.
The cells collected from each group were altered in the lab to revert to stem cells, which were then directed to differentiate into various cell types. The researchers subjected the resulting organoids to ultrasonic waves to simulate some effects of TBIs, such as brain cell death and alterations in tau protein levels, which are linked to Alzheimer’s disease.
Moreover, the team observed changes in a protein known as TDP-43, which has previously been associated with TBIs and numerous neurodegenerative conditions. This protein, typically confined to the nucleus of healthy cells, plays a role in regulating protein synthesis from DNA instructions. However, in neurodegenerative disorders, TDP-43 aggregates into clusters.
The new study implies that, following a TBI, dysfunctional TDP-43 proteins harm and eliminate brain cells. The research team discovered that these proteins may malfunction due to their migration from the nucleus.
These detrimental alterations in TDP-43 were more pronounced in organoids grown from cells of individuals with ALS or dementia compared to those from healthy donors. This suggests that TBIs may pose a higher risk to those with a genetic predisposition to dementia due to this mechanism.
Subsequently, the team explored methods to prevent or reverse these injuries. “We then tested every gene in the human genome to see if we could mitigate that injury by suppressing any individual gene,” stated Justin Ichida, the senior author and an associate professor of stem cell biology and regenerative medicine at the University of Southern California, inResearch Shows New Potential for Treating Traumatic Brain Injuries
A recent study has uncovered a promising development in the field of traumatic brain injury (TBI) treatment. Scientists have identified a gene called KCNJ2, responsible for a cell surface protein, which, when deactivated, offers protection against the harmful effects of TBIs. Through experiments conducted on organoids and laboratory mice, the researchers consistently observed positive outcomes.
According to Ichida, one of the researchers involved in the study, targeting the KCNJ2 gene could potentially help in preventing nerve cell death following a TBI. This discovery holds promise for both post-injury treatments and prophylactic measures, especially for individuals at a higher risk of sustaining a TBI, such as athletes.
While these findings are encouraging, further studies are necessary to transition this potential treatment from organoids to human subjects.
FAQs
1. What is the significance of the KCNJ2 gene in TBI treatment?
The KCNJ2 gene, responsible for a cell surface protein, shows promise in protecting against the harmful effects of traumatic brain injuries when deactivated. This discovery could lead to advancements in TBI treatment strategies.
2. How could targeting the KCNJ2 gene benefit individuals at risk of TBIs?
By targeting the KCNJ2 gene, researchers aim to reduce nerve cell death post-TBI. This approach holds potential for both post-injury treatments and preventive measures for individuals at high risk of sustaining traumatic brain injuries.
3. What are the next steps following these research findings?
While the results are promising, further studies are required to translate these findings from organoids and animal models to human patients. Continued research is essential to validate the efficacy and safety of targeting the KCNJ2 gene in TBI treatments.
