Identification of Glyoxalase-I as a Protein Marker in a Mouse Model of Extremes in Trait Anxiety

Krömer, Simone A.; Keßler, Melanie; Milfay, Dale; Birg, Isabel; Bunck, Mirjam; Czibere, Ludwig; Panhuysen, Markus; Pütz, Benno; Deussing, Jan M.; Holsboer, Florian; Landgraf, Rainer; Turck, Christoph W.

doi:10.1523/jneurosci.0115-05.2005

Cited by 241 publications

(298 citation statements)

References 46 publications

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“…Animals for the following studies were inbred high (HAB) and low (LAB) anxiety-related behavior mice [10][11][12] or unselected outbred CD1 controls (Charles River Laboratories, Sulzfeld, Germany). All mice were tested for parameters indicative of anxietyrelated and depression-like behaviors as well as locomotor activity on the elevated plus-maze (EPM), in the tail-suspension test and in the open field.…”

Section: Human Tmem132d Expressionmentioning

confidence: 99%

“…All mice were tested for parameters indicative of anxietyrelated and depression-like behaviors as well as locomotor activity on the elevated plus-maze (EPM), in the tail-suspension test and in the open field. 10 The animal studies were both approved by the local authorities and conducted according to current regulations for animal experimentation in Germany and the European Union (European Communities Council Directive 86/609/EEC).…”

Section: Human Tmem132d Expressionmentioning

confidence: 99%

“…Furthermore, to test for complementary inter-species effects, the clinical data were supported and extended by expression and association analyses in a mouse model of extremes in trait anxiety. [10][11][12] …”

Section: Introductionmentioning

confidence: 99%

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TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies

et al. 2010

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The lifetime prevalence of panic disorder (PD) is up to 4% worldwide and there is substantial evidence that genetic factors contribute to the development of PD. Single-nucleotide polymorphisms (SNPs) in TMEM132D, identified in a whole-genome association study (GWAS), were found to be associated with PD in three independent samples, with a two-SNP haplotype associated in each of three samples in the same direction, and with a P-value of 1.2eÀ7 in the combined sample (909 cases and 915 controls). Independent SNPs in this gene were also associated with the severity of anxiety symptoms in patients affected by PD or panic attacks as well as in patients suffering from unipolar depression. Risk genotypes for PD were associated with higher TMEM132D mRNA expression levels in the frontal cortex. In parallel, using a mouse model of extremes in trait anxiety, we could further show that anxiety-related behavior was positively correlated with Tmem132d mRNA expression in the anterior cingulate cortex, central to the processing of anxiety/fear-related stimuli, and that in this animal model a Tmem132d SNP is associated with anxiety-related behavior in an F2 panel. TMEM132D may thus be an important new candidate gene for PD as well as more generally for anxiety-related behavior.

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Section: Human Tmem132d Expressionmentioning

confidence: 99%

Section: Human Tmem132d Expressionmentioning

confidence: 99%

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TMEM132D, a new candidate for anxiety phenotypes: evidence from human and mouse studies

et al. 2010

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“…The set up for DL was as previously described (Kromer et al, 2005) using 10 and 300-400lux for the dark and illuminated areas, respectively. Each mouse was placed in the corner of the darkened compartment facing away from the aperture.…”

Section: Behavioral Phenotypingmentioning

confidence: 99%

“…To elucidate the molecular underpinnings of anxiety traits, we have compared mice selectively inbred for ∼ 45 generations for high (HAB) or low anxiety-related behavior (LAB) according to their performance on the elevated plus maze (Kromer et al, 2005). Using a hypothesis-free systems biology platform based on proteomics, metabolomics, and bioinformatics Frank et al, 2009;Haegler et al, 2009;Zhang et al, 2009), we identified alterations in multiple mitochondrial pathways in high anxiety.…”

Section: Introductionmentioning

confidence: 99%

Selective Mitochondrial Targeting Exerts Anxiolytic Effects In Vivo

Nussbaumer

Asara

Teplytska

et al. 2015

Neuropsychopharmacol

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Current treatment strategies for anxiety disorders are predominantly symptom-based. However, a third of anxiety patients remain unresponsive to anxiolytics highlighting the need for more effective, mechanism-based therapeutic approaches. We have previously compared high vs low anxiety mice and identified changes in mitochondrial pathways, including oxidative phosphorylation and oxidative stress. In this work, we show that selective pharmacological targeting of these mitochondrial pathways exerts anxiolytic effects in vivo. We treated high anxiety-related behavior (HAB) mice with MitoQ, an antioxidant that selectively targets mitochondria. MitoQ administration resulted in decreased anxiety-related behavior in HAB mice. This anxiolytic effect was specific for high anxiety as MitoQ treatment did not affect the anxiety phenotype of C57BL/6N and DBA/2J mouse strains. We furthermore investigated the molecular underpinnings of the MitoQ-driven anxiolytic effect and found that MitoQ treatment alters the brain metabolome and that the response to MitoQ treatment is characterized by distinct molecular signatures. These results indicate that a mechanism-driven approach based on selective mitochondrial targeting has the potential to attenuate the high anxiety phenotype in vivo, thus paving the way for translational implementation as longterm MitoQ administration is well-tolerated with no reported side effects in mice and humans.

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