Researchers have discovered that quelling star-shaped brain cells called astrocytes could fight the long-term effects of traumatic brain injury, pointing to a protein involved in the process that could serve as a potential therapeutic target.
Researchers at the Gladstone Institutes in San Francisco discovered that preventing astrocytes from damaging a brain region known as the thalamus improved recovery outcomes in a mouse model, according to a study published July 6 in Science Translational Medicine.
Traumatic brain injuries can often cause high levels of neuroinflammation, which can be both hurtful and helpful in the recovery process. While inflammation can prompt an anti-inflammatory response, it can also cause more damage to sensitive areas, such as the thalamus. Recent findings about the thalamus—which sends and processes sensory and motor signals—suggest damage to this area may lead to sleep disruptions, seizures and other neurological complications.
There have also been reports of lesions in the thalamus among patients who have had neurological issues linked to viral infections, including from COVID-19. However, the extent to which thalamic inflammation is involved in cognitive deficits remains unknown, making the injuries challenging to treat.
Against this backdrop, the research team studied mice to figure out how astrocytes affect neurons and cognitive patterns in the thalamus after brain injury. After inducing inflammation in the thalamus, the mice experienced seizures and increased neuronal excitability akin to what is typically seen in the wake of brain injuries.
Within the astrocytes, the researchers observed that inflammation stifled the expression of GAT3, a protein that transports the neurotransmitter GABA. When they restored GAT3 activity in astrocytes in the thalamus, the mice experienced fewer seizures and saw improved survival rates.
Targeting astrocytes in the thalamus may prevent negative brain injury outcomes, suggested the researchers, although they added further research is needed to understand whether it’s possible to safely target GAT3 for therapeutic effects without compromising the benefits of neuroinflammation.
The scientists aren’t the only ones taking a closer look at astrocytes. A team with the Institute for Basic Science’s Center for Cognition and Sociality in South Korea are examining the role these brain cells play in the progression of Alzheimer’s disease. The researchers recently published findings that show astrocyte-specific gene silencing of the enzyme ornithine decarboxylase 1 (ODC1) can stop excessive GABA production and neuronal inhibition in the hippocampus. After shutting down ODC1, mice performed better in memory-related behavioral tasks, almost completely recovering from disease-related loss of memory. If translated in human models, ODC1 holds the potential to become a new therapeutic target against Alzheimer’s, the researchers suggested.