Molecule linked to permanent “scar” in brain of the depressed
and World Science staff
Researchers say that using mice, they may have pinpointed molecular changes in the brain linked to the psychological “scar” that can haunt depressed people.
Existing medicines don’t reverse these changes, possibly explaining why their effects are temporary, the scientists said.
The researchers induced a depression-like social withdrawal syndrome in mice by exposing them to repeated bouts of social stress. They repeatedly confined these 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 compensatory mechanism in which molecular activators attach themselves to the gene and overcome the silencer molecules.
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