The aim of the study was to better understand how current antidepressants work in the brain. The ultimate goal is to find new ones that are more effective for people not currently getting relief from existing drugs.
In the study, scientists discovered for the first time that antidepressant drugs such as Prozac and tricyclics target a pathway in the hippocampus called the BMP signaling pathway. A signaling pathway is a group of molecules in a cell that work together to control one or more cell functions. Like a cascade, after the first molecule in a pathway receives a signal, it activates another molecule and so forth until the cell function is carried out.
Researchers showed that Prozac and tricyclics inhibit this pathway and, thereby, trigger stem cells in the brain to produce more neurons. These particular neurons are involved in mood and memory formation. But the scientists didn't know if blocking the pathway contributed to the drugs' antidepressant effect because Prozac acts on multiple mechanisms in the brain.
After confirming the importance of the BMP pathway in depression, Northwestern scientists tested a brain protein, Noggin, on depressed mice. Noggin is known block the BMP pathway and stimulate new neurons, called neurogenesis.
They discovered Noggin blocks the pathway more precisely and effectively than Prozac or tricyclics. It had a robust antidepressant effect in mice.
Scientists injected Noggin into the mice and observed the effect on mood by testing for depression and anxiety behavior. A sign of depression in mice is a tendency to hang hopelessly when held by the tail, rather than trying to get upright. After receiving Noggin, mice energetically tried to lift themselves up, whereas control mice were more likely to give up and become immobile.
The mice were then put in a maze with secluded (safe) and open (less safe) spaces. The Noggin mice were less anxious and explored more mazes than the control mice.