November 2011

MCP: Proteomic and metabolic basis for anxiety and depression

MCP_cover

Psychiatric disorders, such as anxiety and depression, have complicated molecular foundations that involve dysfunctional neural circuits.

“The characterization of these altered networks and neural circuits will be critical to get a better understanding of psychiatric disorders and, in turn, make it possible to define targets for the development of more specific medicines,” explains Chris Turck of the Max Planck Institute of Psychiatry in Germany. He adds there presently aren’t any biomarkers for psychiatric illnesses that could help with accurate diagnosis, tracking treatment efficacy in various types of psychiatric patients, and improving drug development efforts.

To address this issue, Turck and colleagues recently compared the proteins and small molecules expressed in two mouse models to identify potential biomarkers. Their results were published in Molecular and Cellular Proteomics. One mouse strain was selectively bred to be a high-anxiety model while the other was a low-anxiety model.

For the proteomic analysis, Turck and colleagues fed a diet that was laced with a stable isotope to these mice. After the animals’ phenotypes had been determined by exposing them to assays to assess anxiety and depression characteristics, the researchers analyzed brain sections and plasma molecules from the mice that were now labeled with the stable isotope by quantitative mass spectrometry.

Turck and colleagues identified a number of proteins and small molecules that belonged to several metabolic, signaling and neural pathways. For example, the researchers found that some proteins and metabolites of the phosphatidylinositol signaling pathway had altered expression levels in the high-anxiety mouse model.

The group has also extended the stable-isotope metabolic labeling method to protein turnover analysis, which will provide more information on pathways affected in anxiety and depression. Ultimately, the researchers want to use several molecules in clinical diagnostic assays instead of a single biomarker, because an individual molecule may not be specific and sensitive enough to accurately monitor a disease.

Rajendrani Mukhopadhyay, Ph.D., (rmukhopadhyay@asbmb.org) is the senior science writer for ASBMB Today and technical editor for JBC. 


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