Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal
Journal of Clinical Investigation. 2012 June 1; 122(6): 2306–2315. Published online 2012 May 15. doi: 10.1172/JCI61319
Article by Margaret G. Distler, Leigh D. Plant, Greta Sokoloff, Andrew J. Hawk, Ivy Aneas, Gerald E. Wuenschell, John Termini, Stephen C. Meredith, Marcelo A. Nobrega, Abraham A. Palmer
Full online text can be viewed here.
Since the 1950's, anxiety disorders have been treated using psychoactive drugs called benzodiazepines. These drugs inhibit neural activity, literally “calming one's nerves.” Benzodiapines are fast-acting to offset anxiety attacks, and are commonly prescribed to patients diagnosed with panic disorder, post-traumatic stress disorder, social phobias, and other diseases characterized by anxiety. Unfortunately, these medications have dangerous side effects like sedation and hypothermia, and high abuse rates due to euphoric response. A study published in June 2012 may provide a new direction to decrease anxiety without the negative side effects of benzodiazepines.
Researchers at the University of Chicago have been examining a link between the gene glyoxalase 1 (Glo1) and anxiety-like behavior in mice. The connection is now clear: anxiety relates to concentration of the compound that Glo1 metabolizes, methylglyoxal or MG. MG is a byproduct of metabolism which is usually broken down since it is toxic to cells at high levels. Surprisingly, the U of Chicago study discovered that MG binds to neuronal receptors inhibiting neuron signaling like anti-anxiety drugs. When MG was injected into mice, they were less anxious.
The Glo1 and MG genes have been studied in great detail for their roles in aging, diabetes, and cancer, but these newly discovered roles are an angle for anxiety treatment worth investigating. Controlling function of Glo1 could alter a process that already takes place in cells. Understanding the role of Glo1 in the central nervous system may contribute to research of other central nervous system diseases such as autism and schizophrenia.
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Last updated: 5-14-2013
University of Wisconsin - Madison
Last updated: 5-14-2013
University of Wisconsin - Madison