Researchers Identify Key Brain Cell in Antidepressant Action

Antidepressant medications such as Prozac have helped improve mood and lessen anxiety in millions of people with major depression. But scientists know surprisingly little about how these drugs work.Now researchers have discovered that a specific type of cell in the outer layers of the brain is crucial for Prozac's action. The study, a collaboration led by Howard Hughes Medical Institute investigator Nathaniel Heintz and Paul Greengard, both at Rockefeller University, is the first demonstration that genetic profiling of specific neural cell types can lead to new insights into the cause of brain disease. The study is published in the May 25, 2012, issue of the journal Cell.“There may be many different cell types whose activity you can alter to have a beneficial impact in depression, and this is one of them," says Heintz. More broadly, he says, "it's proof-of-concept that this approach can give you tremendous information about both the causes of disease and strategies for treatment."Brain scanning studies over the past decade or so have revealed abnormal patterns of neural activity in people with major depression. More specifically, electrical activity in the front of the brain, which is responsible for reasoning and attention, seems to be out of balance with activity in deeper regions involved in regulating emotions in those individuals.After many months of use, antidepressants called selective serotonin reuptake inhibitors, or SSRIs, can gradually balance out those brain signals. These drugs increase the amount of serotonin, a chemical messenger, outside of cells. But low serotonin doesn't cause depression, and no one knows why increasing the chemical leads to positive effects."These SSRIs increase serotonin in many places in the brain," Heintz says. "So the question is, how do they have such a strong clinical impact on one particular aspect of behavior?"The answer, according to two decades of work in Heintz's lab, lies in the remarkable diversity of cells in the brains of humans and other mammals. According to classical studies and his team’s findings, he estimates that there are roughly 500 cell types, from the classic pyramidal neurons that fire off electrical impulses, to inhibitory interneurons that block these signals, to microglia that trigger an immune response during injury or infection. Each cell type may respond differently to specific genetic mutations, environmental exposures, and drugs."Some cells deal with a specific situation just fine, they adjust and compensate and their function is normal," Heintz says. "But some cell types can't do that, and as a result, they cause disruptions in a circuit."Read more at...HHMI News, May 2012.