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Discovery hints at why stress is more devastating for some
Date:9/2/2014

fundamental that it emerged even before the mice were subjected to stress, with some unstressed mice showing an anxiety-like preference for a dark compartment over a lighted one.

The researchers found that the highly stress-susceptible mice had less of an important molecule known as mGlu2 in a stress-involved region of the brain known as the hippocampus. The mGlu2 decrease, they determined, resulted from an epigenetic change, which affects the expression of genes, in this case the gene that codes for mGlu2.

"If you think of the genetic code as words in a book, the book must be opened in order for you to read it. These epigenetic changes, which affect histone proteins associated with DNA, effectively close the book, so the code for mGlu2 cannot be read," says first author Carla Nasca, postdoc in the lab and a fellow of the American Foundation for Suicide Prevention. Previously, she and colleagues first implicated mGlu2 in depression when they showed that a promising potential treatment known as acetyl carnitine rapidly alleviated depression-like symptoms in rats and mice by reversing these epigenetic changes to mGlu2 and causing its levels to increase.

"Currently, depression is diagnosed only by its symptoms," Nasca says. "But these results put us on track to discover molecular signatures in humans that may have the potential to serve as markers for certain types of depression. Our work could also lead to a new generation of rapidly acting antidepressants, such as acetyl carnitine, which would be particularly important to reduce the risk of suicide."

A reduction in mGlu2 matters because this molecule regulates the neurotransmitter glutamate. While glutamate plays a crucial role relaying messages between neurons as part of many important processes, too much can lead to harmful structural changes in the brain.

"The brain is constantly changing. When stressful experiences lead to anxiety and depressive disorders the brai
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Contact: Zach Veilleux
veillez@rockefeller.edu
212-327-8982
Rockefeller University
Source:Eurekalert  

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