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Deleting Gene Makes Stressed Mice Social: Study

Posted on: Saturday, 11 February 2006, 09:00 CST

Deleting gene makes stressed mice social: study

LOS ANGELES, Feb. 9 (Xinhua)-- Deleting a definite gene in brain could cure the bullied or stressed mice just like antidepressants, U.S. scientists reported on Thursday.

In the Feb. 10 issue of the journal Science, scientists said a neurotrophic factor BDNF, which is normally active in the brain, must be present within the brain's dopaminergic regions for the stressed mice to become socially averse to others.

Mice are normally social animals, easily approaching and greeting strangers. However, when the strange mice are aggressive, a mouse over time becomes timid and withdrawn.

Administering antidepressants improves their behavior, but so does deleting a gene called BDNF, said the researchers.

The results could establish an essential role for BDNF in mediating long-term neural and behavioral changes from stressful social situations, they noted.

This study could also help in research into such human conditions as long-term depression or post-traumatic stress disorder, in which social withdrawal is a common symptom.

"This study provides new evidence of the importance of reward pathways in the brain in an animal's responses to social stress, and by extension to depression," said Eric Nestler, the study's senior author at the University of Texas Southwestern Medical Center.

"It also provides some insight into the underlying molecular events involved."

In the experiment, the researchers exposed mice to daily bouts of "social defeat," in which they encountered aggressive mice that overcame them in fights.

This training went on for 10 days. The mice eventually became " defeated," no longer approaching unfamiliar mice. Even four weeks later, the defeated mice avoided other mice, not only their former bullies but even smaller and more docile mice.

In examining the role of BDNF, a type of nerve growth factor, in the mice's behavior, the researchers concentrated on two connected areas of the brain involved in pleasure and addiction: the ventral tegmental area, a dopamine-rich center in the primitive part of the brain, and the nucleus accumbens, a small area in the front part of the brain that receives strong dopamine signals from the ventral tegmental area.

Normal mice have BDNF in the ventral tegmental area, and a minimal amount in the nucleus accumbens, while the "defeated" mice showed an increased amount of BDNF in the nucleus accumbens, the researchers found.

They hypothesized that the ventral tegmental area may be the source of BDNF in the nucleus accumbens and that this BDNF is important in shaping behavior. To test this possibility, the researchers used viral gene transfer to delete the BDNF gene in the ventral tegmental area.

Mice lacking the gene became no longer depressed when exposed to bullies, showing that BDNF signals from the ventral tegmental area to the nucleus accumbens are critical for animals to learn aspects of social experiences.

And this effect was similar to chronic treatment of antidepressants, the researchers said.

"Gene profiling in the nucleus accumbens indicates that local knockdown of BDNF obliterates most of the effects of repeated aggression on gene expression within this circuit, with similar effects being produced by chronic treatment with antidepressant," they wrote in the Science paper

"These results establish an essential role for BDNF in mediating long-term neural and behavioral plasticity in response to aversive social experiences."

Source: Xinhua News Agency - CEIS

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