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Yeast cell reaction to Zoloft suggests alternative cause, drug target for depression
Date:4/24/2012

Princeton University researchers have observed a self-degradation response to the antidepressant Zoloft in yeast cells that could help provide new answers to lingering questions among scientists about how antidepressants work, as well as support the idea that depression is not solely linked to the neurotransmitter serotonin.

In findings published in the journal PLoS ONE, researchers based in the lab of Ethan Perlstein, an associate research scholar in Princeton's Lewis-Sigler Institute for Integrative Genomics and senior lecturer in molecular biology, report that sertraline trademarked as Zoloft accumulated in the internal membranes of baker's yeast cells.

This buildup caused a swelling and sharp curvature in the membranes of vesicles, bubble-like cell components with a hand in cell metabolism, movement and energy storage. The vesicles then went into autophagy, a protective response in which cells recycle excess or damaged membrane.

But yeast cells lack serotonin, which is the primary target of antidepressants, Perlstein said. By observing a reaction to sertraline in an organism that does not contain the drug's conventional target, Perlstein and his co-authors have found significant evidence suggesting that antidepressants engage in pharmacological activity beyond regulating serotonin. Perlstein worked with co-first authors Jingqui Chen and Daniel Korostyshevsky, as well as Sean Lee, all three senior research specialists in Perlstein's lab.

[Images can be seen at http://www.princeton.edu/main/news/archive/S33/52/72E11. To obtain high-res images, contact Princeton science writer Morgan Kelly, (609) 258-5729, mgnkelly@princeton.edu]

Although antidepressants are known to regulate serotonin, it is not completely understood how antidepressants interact with the body's brain cells and what effect,
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Contact: Morgan Kelly
mgnkelly@princeton.edu
609-258-5729
Princeton University
Source:Eurekalert  

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