CUMC Researchers Discuss Enzyme That Affects Mood and Behavior

In an editorial in a recent issue of Cell, Rene Hen, PhD, and Liam J. Drew, PhD, of Columbia’s Department of Psychiatry and the New York State Psychiatric Institute, comment on a paper, published in the same issue of Cell, which finds a novel link between the enzyme called sirtuin (SIRT1) and animal mood and behavior. SIRT1 has been proposed as a potential drug treatment for diabetes, cancer, heart and Alzheimer’s disease. In the case of neurobiology, Hen and Drew say that the enzyme is only one piece of a larger puzzle.

In the paper under discussion, Sergiy Libert and Leonard Guarante, of MIT, and colleagues propose that SIRT1 positively modulates monoamine oxidase A (MAO-A), a focus of mood disorder research since the 1950s, when MAO inhibitors became the first widely used antidepressant drugs.

When caloric intake is low, activity levels of sirtuins rise. Libert and his colleagues found that restricting calories increased MAO levels and that the higher MAO levels were associated with increased anxiety. In their study, treatment with an MAO inhibitor (i.e., an antidepressant) reduced anxiety in mice with high SIRT1 levels.

Sirtuins are key regulators of cellular metabolism. Hen and Drew point out that these enzymes have also been implicated in numerous aspects of neurobiology, including synaptic plasticity and cognition, hypothalamic control of energy intake, and responses to cocaine.

“Food for Thought: Linking Caloric Intake to Behavior via Sirtuin Activity” appeared in the December 23, 2011 issue of Cell.