Researchers have honed in on the mechanism by which antidepressant drugs like Prozac work, and in doing so have identified a pathway for the treatment of depression, anxiety, and other mental health issues. Their research also revealed that a brain protein called noggin (seriously) may be more effective than existing medications at activating this pathway, and could therefore provide the basis for future drugs.
Several antidepressants are known to stimulate the creation of new neurons – or neurogenesis – in a brain region called the hippocampus, which is involved in memory and emotion. However, scientists have struggled to figure out exactly how these drugs bring about this effect.
To investigate, a team of researchers treated lab mice with a medication called fluoxetine – the generic name for Prozac – and found that, among other things, it blocked the activity of a protein called hippocampal bone morphogenetic protein (BMP). Normally, when BMP binds to certain brain receptors, it sparks off a series of events that are thought to contribute to the creation of new neurons.
Explaining this finding in the journal Molecular Psychiatry, the study authors reveal that fluoxetine causes this effect by increasing the production of the protein noggin, which is a known BMP inhibitor. This led them to wonder if noggin itself could be used as an antidepressant.
Noggin blocks MBP, resulting in the creation of new neurons in the hippocampus. Andrii Vodolazhskyi/Shutterstock
In an attempt to clarify this, they injected noggin into the brains of mice that had been engineered to suffer from depression, and found that this sparked a massive increase in hippocampal neurogenesis, superior to that seen with most antidepressant drugs. This then led to a significant decrease in depressive symptoms, which the researchers measured using a series of standardized tests.
One of these tests involved holding the mice by the tail and observing whether they had the motivation to try and wriggle free, or simply gave up and dangled helplessly. After being injected with noggin, depressed mice became much more wriggly than those that didn’t receive a shot of the protein, indicating that they had become less forlorn.
In another experiment, mice were placed in a maze with both covered and open sections. Sticking to the sheltered areas rather than exploring the exposed regions is taken as a sign of anxiety, and this tendency was majorly reduced in mice that received noggin.
All in all, the study authors believe that by inhibiting BMP signaling, noggin is responsible for the antidepressant effects of drugs like Prozac, and that targeting this specific pathway could yield more effective treatments for depression.