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Vulnerability to Stress Linked to Brain Molecule
Date:10/18/2007

he stress of the situation, while others avoided contact and showed submissive behavior.

The researchers then made detailed studies of two brain regions -- the ventral tegmental area (VTA) and the nucleus accumbens (NAcc), which are part of the brain's reward area that promotes acts that aid in survival. They found that the excess BNDF production in vulnerable mice occurred in the VTA but not the NAcc region. Chemical signals sent by the protein from the VTA to the NAcc made the mice vulnerable to stress. Experimental compounds that blocked those signals turned vulnerable mice into resistant mice.

The findings, published online Oct. 18 in the journal Cell, raise the possibility of "tools to develop things in the brain that encourage resilience, to help people with stress," Nestler said.

"We have always tried to understand the changes in the brain that lead to such things as the symptoms of post-traumatic stress disorder," Krishnan added. "This study shows we can increase our understanding and development of new therapeutic measures to overcome those changes."

But new therapies might not be easy to develop, Nestler said, since a decrease of dopamine or BDNF activity might be helpful in one part of the brain but harmful in another area.

Dr. Thomas R. Insel, director of the U.S. National Institute of Mental Health, which funded the research, said the findings are "part of a large body of work coming out of Dr. Nestler's laboratory trying to understand what this important neurotrophic molecule, BDNF, does."

"What's exciting here is that it is important for resilience, being able to recover from a traumatic event," Insel added. "One of the great values of this work is to help us understand how mammals, including humans, might be able to recover from the traumas inherent in human existence."

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