Mice offer clues to the roots of human resilience
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The findings could point to new psychiatric drugs, and perhaps even new ways to encourage resilience for people in high-stress circumstances, including soldiers in combat, disaster relief workers, and disaster victims, according to the researchers.
They found that mice who are more susceptible to social defeat show increased levels of a growth factor known as brain-derived neurotrophic factor (BDNF) in a portion of the brain integral to reward- and emotion-related behaviors.
Nestler said.
In addition to their lonely lifestyle, the susceptible mice showed significant weight loss and less interest in sugar, both of which are consistent with a depression-like state, they reported. The more vulnerable mice also showed greater sensitivity to a low dose of cocaine, among other abnormalities.
Indeed, they found evidence that dopamine neurons of animals susceptible to social stress fire at a faster rate than those of more resilient animals do. They also report that a less active form of BDNF lends mice greater toughness following socially stressful conditions.
Finally, they found, the postmortem brain tissue of patients who had been depressed showed a 40 percent increase in BDNF compared to unaffected individuals, suggesting that the results in mice may have clinical relevance. Nestler said that any of the genes found to differ in activity between the brains of susceptible and resilient mice could be drug targets for those suffering the affects of acute stress.
The researchers include Vaishnav Krishnan, Ming-Hu Han, Danielle L. Graham, Olivier Berton, William Renthal, Scott J. Russo, Quincey LaPlant, Ami Graham, Michael Lutter, Diane C. Lagace, Subroto Ghose, Robin Reister, Paul Tannous, Thomas A. Green, of The University of Texas Southwestern Medical Center (UTSWMC) in Dallas; Rachael L. Neve of the Department of Genetics and McLean Hospital, Harvard University in Cambridge; Sumana Chakravarty, Arvind Kumar, Amelia J. Eisch, David W. Self, of The University of Texas Southwestern Medical Center (UTSWMC) in Dallas; Francis S. Lee, of Weill Medical College of Cornell University in New York; and Carol A. Tamminga, Donald C. Cooper, Howard K. Gershenfeld, and Eric J. Nestler of The University of Texas Southwestern Medical Center (UTSWMC) in Dallas.
This was work was supported by grants from The National Institute of Mental Health and The National Institute on Drug Abuse (E.J.N.) and the National Alliance for Research in Schizophrenia and Depression (M.-H.H.).
Krishnan et al.
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