Researchers at the University of California, Riverside announced on Apr. 27 that a single protein, Adgrl2, plays a key role in both the development of neural connections and the maintenance of blood vessel integrity in the brain. The findings were published in the Journal of Neuroscience.
The study addresses how neurons form contact points called synapses to transmit signals while blood vessels create a network that delivers nutrients and controls what enters the brain. The research is significant because it highlights how one molecule can influence two critical systems for healthy brain function.
According to Garret R. Anderson, assistant professor of molecular, cell and systems biology at UC Riverside, "Normally, brain blood vessels form a specialized unit known as the blood-brain barrier, which do not allow certain chemicals in the blood to come in contact with neurons in the brain." Anderson said, "Without Adgrl2, we found that the vessels became leaky and allowed these chemicals to get through. This shows Adgrl2 is essential for maintaining a healthy vascular system in the brain."
The researchers discovered that although both neurons and endothelial cells (cells lining blood vessels) use instructions from the same gene for Adgrl2, they edit these instructions differently before producing their respective proteins. "This process, called alternative splicing, allows different cell types to produce slightly different versions of Adgrl2," Anderson said. "Neurons make one version; endothelial cells make another." When scientists forced endothelial cells to produce the neuronal version instead of their own type-specific variant, those cells began forming contacts similar to synapses rather than supporting normal vascular function.
"It was as if the cells were trying to join the brain's communication network instead of maintaining the vascular system," Anderson said. "The blood vessels became overly restrictive and the barrier that normally regulates what passes from the blood into the brain tightened, disrupting balance between blood and brain. This can increase risk of hydrocephalus—a condition where excess fluid builds up in the brain."
The research was funded by grants from organizations including Whitehall Foundation and Regents Faculty Development Grant from UCR Academic Senate. The team included Alexander King (lead graduate student), Catherine Garcia, Crisylle Blanton, Anna Chen and Amna Ahmad from UC Riverside; David Lukacsovich and Csaba Földy from University of Zurich; Takako Makita from University of South Carolina.
These findings may have broader implications for understanding disorders involving either neural connectivity or disruptions in vascular stability within neurological conditions.
