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Studies seek better understanding and treatment of depression
Date:8/14/2012

AUGUSTA, Ga. Connecting the dots between two molecules whose levels are decreased in depression and increased by current antidepressants could yield new therapies, researchers say.

Serotonin is a neurotransmitter that enables brain cells to communicate and brain-derived neurotropic factor, or BDNF, is a brain-nourishing molecule that also aids connectivity. Popular antidepressants such as Prozac, developed to increase levels of serotonin, have recently been found to also increase BDNF levels, said Dr. Anilkumar Pillai, neuroscientist at the Medical College of Georgia at Georgia Health Sciences University.

"We don't know how the molecule, serotonin, which is well-studied in depression, regulates BDNF signaling," Pillai said. He's principal investigator on a five year, $1.5 million grant from the National Institute of Mental Health to help him make the connection

He suspects a critical piece is the protein transglutaminase 2, or TG2, expressed by brain cells and most other cell types. TG2 plays a role in natural serotonin recycling and potentially is a factor in the serotonin deficiency associated with depression. It also may help explain why levels of serotonin and BDNF seem to rise and fall in sync, Pillai said.

TG2 coverts serotonin to Rac1, a protein that helps rejuvenate BDNF receptors, which typically sit on the surface of brain cells but must periodically move inside to reinvigorate. Depression appears to upset the balance of these complex, critical inner workings. Pillai hypothesizes that the high levels he has found in depression, likely result in too much serotonin conversion leaving too little of the neurotransmitter to properly support brain cell communication. Instead, more Rac1 is produced but inexplicably its degradation also increases ultimately decreasing BDNF signaling as well.

Pillai has seen the unfortunate chain of events play out in an animal model with increased levels of TG2 and clear
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Contact: Toni Baker
tbaker@georgiahealth.edu
706-721-4421
Georgia Health Sciences University
Source:Eurekalert  

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