Chinese researchers identify key protein behind depression

Chinese researchers said Thursday that they have identified a key protein in the brain responsible for the development of depression, offering a fresh avenue in the search for therapies to treat depression.

Previous studies have found that cells in a brain region called lateral habenula (LHB) are hyperactive in depressed individuals, but scientists haven't known what triggers them.

Curious about molecular-scale activity in the LHB of depressed people, the researchers from the Shanghai Institutes for Biological Sciences, part of the Chinese Academy of Sciences, used a technique called quantitative proteomic screening to examine the proteins in the LHB tissue of regular rats and rats that had been depressed since birth.

The researchers reported in the U.S. journal Science that a protein called CaM was nearly twice as abundant in the depressed rats.

When the researchers gave depressed rats antidepressant drugs, not only depressive symptoms of the animals improved significantly, but also the amounts of the protein in the LHB tissue dropped significantly.

To understand what level of the protein might be required in the LHb to cause depressive behavior, they injected variable levels of this protein into regular rats and mice using viral vectors and found LHb cell activity spiked in both animals.

After 10 days, the researchers tested the engineered animals' attentiveness to sugar, a substance typically of interest to rodents, and also put them in forced swim tests to see how willing they were to fight to stay afloat.

They found that animals with very high CaM levels showed less interest than their counterparts in the sugar, and exhibited less "fight" in the swim test -- both symptoms of depression.

Furthermore, depressive symptoms were reversed when the researchers reduced CaM expression using a technique called RNA interference.

"Our study shows that depression could be reversed via regulating a molecule's expression levels in a part of brain," Professor Hailan Hu at the Shanghai Institutes for Biological Sciences, who led the research team, told Xinhua. "Hence, it provides a new potential target for gene therapy of depression."