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Eric Nestler on deltaFosB Research’s Implications for Depression Treatment


Dr. Eric Nestler


Dr. Eric Nestler of the Mt. Sinai School of Medicine explains deltaFosB research and what it could mean for depression treatment


Announcer: NIMH Radio… from Bethesda.

Announcer: Dr. Eric Nestler is with the Mt. Sinai School of Medicine and the leader of a research team funded by the National Institute of Mental Health. Dr. Nestler and his team believe a gene regulator in the brain's reward hub called deltaFosB could lead to development of new treatments for depression.

Dr. Eric Nestler: We were interested in this based on our data with deltaFosB and other models- addiction models and natural reward models where we found that induction of deltaFosB in response to chronic drug exposure or consumption of high volumes of natural rewards like food, high fat, sugar and so on… induced deltaFosB and that deltaFosB induction enhanced an animal's reward status and enhanced their motivation for rewards. That sounded to us something similar to an anti-depressant like response.

Announcer: Triggering deltaFosB protected mice from developing a depression-like syndrome following chronic social stress.

Dr. Eric Nestler: Many depressed humans have too low a level of deltaFosB. That work was done after the people died and we examined their brains at autopsy. We would like to do the same types of studies in living patients.

Announcer: This would require imaging of the brain's reward hub for deltaFosB levels. Experiments in a mouse model of depression showed that inducing deltaFosB in the reward hub is necessary for Prozac's antidepressant effect.

Dr. Eric Nestler: Antidepressant medications that are available today work in part by inducing in the brains of people who are sick some of the same changes that occur naturally in people who are inherently more resilient. And that does provide new, general avenues to develop novel antidepressant medications.

Announcer: The mouse findings have led to high tech screening for molecules in the brain's reward hub that boost deltaFosB levels. This could lead to development of medications that would help people cope with chronic stress and depression. It could also be used in brain imaging to aid in diagnosis and treatment.

Dr. Eric Nestler: The only way the doctor can make a diagnosis of depression is based on what he or she sees and what the patient says. If we could image in the person's brain levels of detaFosB or other proteins that we think are very important in determining depression we can actually say.. yea, you know it looks like your levels of deltaFosB are too low in your reward circuitry and given that molecular lesion here's the medication we think is going to work best for you. Whereas right now those decisions are made essentially without any guidance. Doctors choose one drug or another, essentially by random choice.

Announcer: Dr. Eric Nestler of the Mt. Sinai School of Medicine...on NIMH radio.