Researchers present new targets for treating depression at Neuroscience Annual Meeting

(Press-News.org) Researchers from Mount Sinai School of Medicine are presenting important discoveries on the involvement of the immune system and dopamine cells in the onset of depression at Neuroscience 2012, the Society for Neuroscience's 42nd annual meeting on October 13 -17 in New Orleans, and are available for interviews.

In addition to scientists presenting at the conference, Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean, Mount Sinai School of Medicine, Executive Vice President for Academic Affairs, The Mount Sinai Medical Center, is available to speak about depression and the psychobiological mechanisms of human resistance to stress. As a renowned expert in the neurobiology and treatment of mood and anxiety disorders, he has led research teams that have discovered that ketamine is a rapidly-acting drug in patients with treatment-resistant depression.

Dr. Charney has co-authored a book, Resilience: The Science of Mastering Life's Greatest Challenges, and a recent review article on this topic is featured in this week's issue of the journal Science, found here. The website also includes a podcast on how resilience training may help as a treatment for depression.

Highlights of Mount Sinai research at Neuroscience 2012:

--Inhibiting Dopamine Reduces Symptoms of Depression in an Animal Model: Abstract #522.01, Press Conference on Sunday, October 14, 2012 at 12:30 p.m., Presentation on Tuesday, October 16, 8:00 a.m., Ernest N. Memorial Convention Center. UNDER EMBARGO UNTIL SUNDAY, OCTOBER 14, 2012 AT 12:30 P.M. Central Time

Led by Dipesh Chaudhury, PhD, Associate Scientist, and Jessica Walsh, MSc, in the laboratory of Ming-Hu Han, PhD, in the Department of Pharmacology and Systems Therapeutics at Mount Sinai, researchers evaluated the activity of dopamine neurons in the ventral tegmental area, the brain's reward center. These neurons produce the brain's dopamine, a chemical that regulates reward-seeking behavior.

To assess whether inhibiting dopamine neurons affected depression, the research team modulated dopamine cell activity in mice using a novel technique called optogenetics. Optogenetics allows scientists to engineer molecules that can be targeted to specific neurons, in this case dopamine neurons, and increase or decrease their activity using light.

By increasing the activity of dopamine neurons in already-stressed mice, the researchers produced depressed behavior. Inhibiting the activity of dopamine neurons in depressed mice eased their depression.

"Increasing evidence shows that depression may not only be caused by a chemical imbalance in the brain but also by neuronal misfiring in different areas brain," said Dr. Chaudhury. "By targeting neurons in the reward center of the brain, we were able to demonstrate that this chemical may be a promising target for new treatments for depression."

--Innate Immune System Influences Vulnerability to Anxiety or Depression in Animal Model: Saturday, Oct.13, 3:15 p.m., Room Number: 288 UNDER EMBARGO UNTIL SATURDAY, OCTOBER 13, 2012 AT 3:15 P.M. Central Time

Scientists have hypothesized that depression results from an inflammatory response in the brain, indicating some immune system involvement. Led by Georgia Hodes, PhD, a Postdoctoral Fellow in the laboratory of Scott Russo, PhD, in the Department of Neuroscience at Mount Sinai, a team of researchers tested this hypothesis by evaluating a cytokine called interleukin-6, which is a protein released by white blood cells in response to injury and is found in elevated levels in people with treatment-resistant depression. They found no evidence of interleukin-6 being made in the brain areas examined, suggesting that it is released in the peripheral immune system.

Next, the Mount Sinai team transplanted the bone marrow of depressed mice into healthy mice and found that these previously healthy mice exhibited signs of depression after experiencing a mild stressor. They also found that mice with immune cells that release more interleukin-6 in response to a toxin developed a more severe depression-like response to the stress.

"To our knowledge, this is the first study showing a functional role for the peripheral immune system in an animal model of depression," said Dr. Hodes. "This study suggests that cytokine-based antibody therapy currently approved for treatment of inflammatory illnesses such as rheumatoid arthritis and Castleman's disease in humans may have potential as an antidepressant treatment."

### Other researchers involved in Dr. Hodes work include Miriam Merad, PhD, Marilyn Lebouef, MS, and graduate students Madeline Pfau, Daniel Christoffel, Sam Golden, and MD/PhD student Mitra Heshmati.

The Mount Sinai Medical Center is one of the world's leading institutions in discovering better ways to prevent, diagnose and treat serious brain diseases. Mount Sinai's Department of Neuroscience ranks number five in the nation for National Institutes of Health (NIH) funding, and its work in multiple sclerosis (MS) has been recognized with more than $44 million in NIH research grants—the largest amount ever awarded by NIH for MS.

The Mount Sinai Medical Center is one of just five locations in the United States using new combined MRI/PET technology to image the brain with an unprecedented level of precision to find more effective interventions for addiction, Alzheimer's disease, depression, multiple sclerosis, and other debilitating diseases.

Dr. Chaudhury's research was supported by the National Institute of Mental Health and a Johnson & Johnson/IMHRO Rising Star Translational Research Award.

Dr. Hodes' research was supported by the National Institute of Mental Health, Johnson & Johnson/IMHRO Rising Star Translational Research Award, and an institutional training grant from the National Institute on Drug Abuse.

About The Mount Sinai Medical Center The Mount Sinai Medical Center encompasses both The Mount Sinai Hospital and Mount Sinai School of Medicine. Established in 1968, Mount Sinai School of Medicine is one of the leading medical schools in the United States. The Medical School is noted for innovation in education, biomedical research, clinical care delivery, and local and global community service. It has more than 3,400 faculty in 32 departments and 14 research institutes, and ranks among the top 20 medical schools both in National Institutes of Health (NIH) funding and by US News and World Report.

The Mount Sinai Hospital, founded in 1852, is a 1,171-bed tertiary- and quaternary-care teaching facility and one of the nation's oldest, largest and most-respected voluntary hospitals. In 2011, US News and World Report ranked The Mount Sinai Hospital 14th on its elite Honor Roll of the nation's top hospitals based on reputation, safety, and other patient-care factors. Mount Sinai is one of 12 integrated academic medical centers whose medical school ranks among the top 20 in NIH funding and US News and World Report and whose hospital is on the US News and World Report Honor Roll. Nearly 60,000 people were treated at Mount Sinai as inpatients last year, and approximately 560,000 outpatient visits took place. For more information, visit http://www.mountsinai.org/.

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