New anti-depressant mechanisms in brain identified

Researchers at UT Southwestern Medical Center has identified a major mechanism by which ghrelin (a hormone with natural anti-depressant properties) works inside the brain.

Simultaneously, the researchers identified a potentially powerful new treatment for depression in the form of a neuroprotective drug known as P7C3.

Dr. Jeffrey Zigman, Associate Professor of Internal Medicine and Psychiatry at UT Southwestern, and co-senior author of the study, said by investigating the way the so-called 'hunger hormone' ghrelin works to limit the extent of depression following long-term exposure to stress, they discovered what could become a brand new class of anti-depressant drugs.

The current findings identify ghrelin's ability to stimulate adult hippocampal neurogenesis, the formation of new neurons, in animal models. In addition, Dr. Zigman and his colleagues also found that the regenerative process inside the hippocampus - a region of the brain that regulates mood, memory, and complex eating behaviors - is crucial in limiting the severity of depression following prolonged exposure to stress.

Dr. Zigman said after identifying the mechanism of ghrelin's anti-depressant actions, we investigated whether increasing this ghrelin effect by directly enhancing hippocampal neurogenesis with the recently reported P7C3 class of neuroprotective compounds would result in even greater anti-depressant behavioral effects.

Dr. Andrew Pieper, a former UT Southwestern faculty member and co-senior author of the current study, said they found that P7C3 exerted a potent anti-depressant effect via its neurogenesis-promoting properties. Also exciting, a highly active P7C3 analog was able to quickly enhance neurogenesis to a much greater level than a wide spectrum of currently marketed anti-depressant drugs.

The study has been published online in the journal Molecular Psychiatry.