Methylglyoxal-mediated anxiolysis involves increased protein modification and elevated expression of glyoxalase 1 in the brain

J Neurochem. 2010 Jun;113(5):1240-51. doi: 10.1111/j.1471-4159.2010.06693.x. Epub 2010 Mar 20.


Methylglyoxal (MG) is a highly reactive metabolite that forms adducts with basic amino acid side chains in proteins. MG is degraded by glyoxalase1 (GLO1), an enzyme shown to be differentially expressed in several mouse models of anxiety-related behavior. As yet, molecular mechanisms by which altered GLO1 expression influences emotionality have not been elucidated. Here we report that both MG concentration and protein modification are altered in brain tissue of a mouse model for trait anxiety, with elevated levels in low anxiety-related behavior relative to high anxiety-related behavior animals. Accordingly, repeated intracerebroventricular injections of MG mediated anxiolysis in inbred high anxiety-related behavior and outbred CD1 mice. We found that anxiolytic-like properties of MG were independent of GLO1 expression. In contrast, antidepressant-like properties of intracerebroventricular MG were suppressed in CD1 mice carrying extra copies of the GLO1 gene. Moreover, MG treatment increased expression of GLO1 only in CD1 mice that did not have extra copies of GLO1. Taken together, these results suggest that the MG levels in brain are negatively correlated with anxiety. Thereby, we identified a novel molecular mechanism for anxiety-related behavior in mice that may help to elucidate genesis of psychiatric disorders in humans.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Anxiety Agents*
  • Anxiety / drug therapy
  • Anxiety / psychology
  • Blotting, Western
  • Brain / drug effects
  • Brain / enzymology*
  • DNA / genetics
  • Electrophysiology
  • Excitatory Postsynaptic Potentials / drug effects
  • Gas Chromatography-Mass Spectrometry
  • Gene Dosage / genetics
  • Gene Dosage / physiology
  • Gene Duplication
  • Gene Expression Regulation, Enzymologic / drug effects
  • Hindlimb Suspension
  • Immunohistochemistry
  • Injections, Intraventricular
  • Lactoylglutathione Lyase / biosynthesis*
  • Lactoylglutathione Lyase / genetics*
  • Long-Term Potentiation / drug effects
  • Male
  • Mice
  • Polymorphism, Single Nucleotide
  • Protein Processing, Post-Translational / drug effects*
  • Pyruvaldehyde / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction


  • Anti-Anxiety Agents
  • Pyruvaldehyde
  • DNA
  • Lactoylglutathione Lyase