title: Glyoxalase 1 and glutathione reductase 1 regulate anxiety in mice.
abstract: Anxiety and fear are normal emotional responses to threatening situations. In human anxiety disorders--such as panic disorder, obsessive-compulsive disorder, post-traumatic stress disorder, social phobia, specific phobias and generalized anxiety disorder--these responses are exaggerated. The molecular mechanisms involved in the regulation of normal and pathological anxiety are mostly unknown. However, the availability of different inbred strains of mice offers an excellent model system in which to study the genetics of certain behavioural phenotypes. Here we report, using a combination of behavioural analysis of six inbred mouse strains with quantitative gene expression profiling of several brain regions, the identification of 17 genes with expression patterns that correlate with anxiety-like behavioural phenotypes. To determine if two of the genes, glyoxalase 1 and glutathione reductase 1, have a causal role in the genesis of anxiety, we performed genetic manipulation using lentivirus-mediated gene transfer. Local overexpression of these genes in the mouse brain resulted in increased anxiety-like behaviour, while local inhibition of glyoxalase 1 expression by RNA interference decreased the anxiety-like behaviour. Both of these genes are involved in oxidative stress metabolism, linking this pathway with anxiety-related behaviour.
authors.affiliation: The Salk Institute for Biological Studies, Laboratory of Genetics, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
authors.forename: Iiris
authors.initials: I
authors.lastname: Hovatta
authors.forename: Richard S
authors.initials: RS
authors.lastname: Tennant
authors.forename: Robert
authors.initials: R
authors.lastname: Helton
authors.forename: Robert A
authors.initials: RA
authors.lastname: Marr
authors.forename: Oded
authors.initials: O
authors.lastname: Singer
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Redwine
authors.forename: Julie A
authors.initials: JA
authors.lastname: Ellison
authors.forename: Eric E
authors.initials: EE
authors.lastname: Schadt
authors.forename: Inder M
authors.initials: IM
authors.lastname: Verma
authors.forename: David J
authors.initials: DJ
authors.lastname: Lockhart
authors.forename: Carrolee
authors.initials: C
authors.lastname: Barlow
mesh_terms: D000818:Animals; D001007:Anxiety / Q000201:enzymology* / Q000235:genetics* / Q000503:physiopathology; D001921:Brain / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism*; D007791:Lactoylglutathione Lyase / Q000235:genetics / Q000378:metabolism*; D016086:Lentivirus / Q000235:genetics; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018384:Oxidative Stress / Q000235:genetics; D010641:Phenotype; D014161:Transduction, Genetic
chemical_list: D005980:Glutathione Reductase; D007791:Lactoylglutathione Lyase