“How lithium acts on the brain has been this great mystery of psychopharmacology,” study coauthor Joshua Meisel of MIT said in a statement. “We think that it’s perfectly reasonable to add BPNT1 onto the list of hypotheses for how lithium is affecting the brain,” he said, but cautioned against extrapolating the findings to humans.
In a previous study, Meisel and colleagues found that chemosensory “ASJ” neurons enable the roundworm Caenorhabditis elegans to avoid potentially harmful bacteria. Other research has shown that these neurons are also involved in reviving the worms from the “dauer exit”—a period of starvation-induced hibernation—in the presence of food.
The present study suggests that lithium treatment inhibits ASJ neurons by blocking the activity of BPNT-1. This protein dephosphorylates a compound called PAP, an inhibitor of RNA breakdown. In humans, PAP is found in neurons that produce the stimulatory neurotransmitters dopamine, epinephrine, and norepinephrine.
Future studies are needed to investigate lithium’s mechanism of action in other animals, including humans, the researchers said in the statement.