Scientists shed light on cellular basis of depression

By ANI
Thursday, February 24, 2011

LONDON - Scientists have identified hyperactive cells in a tiny brain structure that may play an important role in depression.

The research, conducted in rats, is helping to reveal a cellular mechanism for depressive disorders that could lead to new, effective treatments.

The study by researchers at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory, Cold Spring Harbor Laboratory, and the University of California, San Diego School of Medicine provides evidence that inhibition of this particular brain region - the lateral habenula - using implanted electrodes can reverse certain behaviors associated with depression, and also provides a mechanism to explain this effect.

These findings lend support to the use of deep brain stimulation as a clinical treatment for people with long-standing, treatment-resistant depression.

“This research identifies a new anatomical circuit in the brain that mediates depression, and shows how it interacts with the brain’s reward system to trigger a constant disappointment signal - which certainly would be depressing,” said Fritz Henn, a neurobiologist and psychiatrist at Brookhaven and Cold Spring Harbor laboratories and a co-investigator on the research. “But,” he added, optimistically, “identifying this circuit and how it works may open new doors to reversing these effects.”

For example, said co-investigator Roberto Malinow, a professor of neurosciences at the UCSD School of Medicine, “it’s possible that the genes specifically expressed in these neurons could be targeted genetically or pharmacologically in order to manipulate them and reduce depression.”

Scientists have known that cells in the lateral habenula are activated by negative or unpleasant events, including punishment and disappointment, such as when you don’t get an expected reward. It may seem intuitive that such negative stimuli can lead to depression, but not everyone who experiences disappointment collapses into a state of helplessness. To explore this connection, the scientists wanted to take a closer look at the brain circuits.

They examined the sensitivity of lateral habenula brain cells - particularly those that connect and send signals to the brain’s reward centers - in two animal models of “learned helplessness,” a form of depression, as well as in control animals that weren’t helpless.

Overall, the scientists found that these lateral habenula nerve cells were hyperactive in the depressed animals but not in the controls. Furthermore, the degree of hyperactivity coincided with the degree of helplessness.

“The activation of the lateral habenula is known to influence the release of serotonin and norepinepherine, two targets of current antidepressant medications,” said Henn. “The current study looked at the role of the lateral habenula in terms of the dopamine system, the system involved in reward signaling. We found that hyperactivity in the lateral habenula due to stress-induced helplessness shuts off the brain’s reward system.”

The study appears in the February 24, 2011, issue of Nature. (ANI)

Filed under: Science and Technology

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