UC study: Signaling pathway in brain helps maintain health, prevent cognitive deficit

While it was previously known that TGF-β signaling helps keep microglia in balance, Luo said it was not known that microglia make the ligands themselves in a “spatially and precisely controlled” manner carried out by each individual cell, a mechanism called autocrine signaling.

“You can think of these microglia cells as being, in a way, ‘selfish,’ as they only make the ligand to keep themselves in balance and not inflamed,” said graduate student and study coauthor Elliot Wegman. “This, thereby, provides a very precise mechanism to regulate local states of inflammation in the microenvironment of the brain.”

Using animal models, the team additionally found that when the TGF-β ligand is genetically deleted from microglia, it leads to global neuroinflammation in the brain. 

“This suggests that the neuroinflammation in microglia is sufficient by itself without other causes to drive cognitive deficit,” Luo said. “We show the direct cause and link between these events.”

Moving forward, the team will investigate whether cognitive deficit can be slowed, stopped or potentially reversed by boosting the TGF-β ligand and signaling pathway in the brain under conditions where TGF-β signaling becomes compromised.

“We’re investigating whether restoring the TGF-β signaling pathway and revitalizing its signaling can then ameliorate disease-related or age-associated cognitive deficits,” she said. “The long-term goal of our research is to modify the brain environment to better support the survival of the neurons or promote repair of the brain after injury or damage.”