Scientists from the RIKEN Center for Life Science Technology (CLST) have developed a new PET scan that is able to analyze neuron proliferation in the brain's subventricular and subgranular zones of the hippocampal dentate gyrus, the areas most affected by depression.
Hippocampal neurogenesis is associated with learning and memory. It is also the most affected by depression and anti-depressive drugs. The process of visualizing how depression and antidepressant drugs affected the brain has been difficult non-invasively. MRIs are able to show the effects, but the process involves injections into the brain. PET imaging using the [18F]FLT molecule as a marker for cell proliferation has struggled to differentiate between regions with and without cell growth.
"We were not exactly sure why this was happening, but surmised that it is because the body actively pumps the molecule out of the brain through the blood-brain barrier, using active transport mechanisms," said Norihisa Tamura, of the CLST. "This means that it is difficult for [18F]FLT to accumulate in the brain in sufficient concentrations to allow effective imaging."
Testing this theory, Tamura and colleagues injected rats with probenecid, which prevents the transport of [18F]FLT outside of the brain. They discovered clear signals in two areas of the brain. These signals decreased as the rats were treated with corticosterone to trigger depression. When the rats were treated with anti-depressives, the rate of cell proliferation increased, meaning the drugs were able to effectively counteract the decreased neurogenesis caused by the corticosterone.
"This is a very interesting finding, because it has been a longtime dream to find a non-invasive test that can give objective evidence of depression and simultaneously show whether drugs are working in a given patient. We have shown that it is possible, at least in experimental animals, to use PET to show the presence of depression and the effectiveness of drugs,” said Yosky Kataoka, who led on the research team. “Since it is known that these same brain regions are involved in depression in the human brain, we would like to try this technique in the clinic and see whether it turns out to be effective in humans as well."