Molecule blamed for 'scar' in brains of the depressed

[Nova]

I realize we, as humans, are not equal to mice.
Still an interesting study.


Nova

Molecule blamed for “scar” in brains of the depressed

March 1, 2006

Courtesy NIH/National Institute of Mental Health and World Science staff

http://www.world-science.net/othernews/060301_scarfrm.htm

Researchers say that using mice, they may have pinpointed molecular changes in the brain linked to a psychological “scar” that can haunt depressed people.

Existing medicines don’t reverse these changes, possibly explaining why they work only temporarily, the scientists said.

The researchers induced a depression-like social withdrawal syndrome in mice by exposing them to social stress. They repeatedly confined the mice with more dominant mice that bullied them. Eventually the “defeated” mice started avoiding all other mice.

Scientists believe this type of experiment may produce a sort of animal version of human depression.


In addition to the social withdrawal, repeated defeat left mice with an enduring “molecular scar” in its brain, the researchers reported, which could help to explain why depression is so hard to cure.


The depression is thought to be linked to a drop in the amount of a protein called BDNF in parts of the brain, the researchers said. This occurs because certain “silencer molecules” turn off the gene that makes BDNF.


When mice were given a conventional antidepressant, imipramine, it temporarily restored BDNF production by activating a compensatory mechanism, the researchers reported. But it didn’t remove the silencer molecules.


This “molecular scar… can’t be easily reversed,” said Eric Nestler of The University of Texas Southwestern Medical Center in Dallas, Texas, leader of the research group. “To really cure depression, we probably need to find new treatments that can remove the silencer molecules.”


The team reported its findings online in the research journal Nature Neuroscience this week.


“Our study provides insight into how chronic stress triggers changes in the brain that are much more long-lived than the effects of existing antidepressants,” said Nestler.


The “silencer molecules” are called methyl groups. They turn off genes by attaching themselves to other molecules called histones, which are wrapped together with DNA and govern the activation and inactivation of specific genes.


The way imipramine helped temporarily, Nestler said, was by triggering a mechanism in which molecular activators attach themselves to the gene and overcome the silencer molecules. >>