Reduced expression of glyoxalase-1 mRNA in mood disorder patients

Fujimoto, Michiko; Uchida, Shinichi; Watanuki, Toshio; Wakabayashi, Yoshiki; Otsuki, Koji; Matsubara, Takehiro; Suetsugi, Masatomo; Funato, Hiromasa; Watanabe, Yoshifumi

doi:10.1016/j.neulet.2008.04.024

Cited by 59 publications

(51 citation statements)

References 29 publications

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“…The present study may also provide mechanistic insight into GLO1's proposed associations with other CNS diseases, such as autism (48,49), affective disorders (50,51), panic disorder (52), and schizophrenia (53). Human genome-wide association studies have identified an association between restless legs syndrome (RLS) and a haplotype containing GLO1 (54,55).…”

Section: Discussionmentioning

confidence: 90%

Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal

Distler¹,

Plant²,

Sokoloff³

et al. 2012

J. Clin. Invest.

132

214

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Glyoxalase 1 (Glo1) expression has previously been associated with anxiety in mice; however, its role in anxiety is controversial, and the underlying mechanism is unknown. Here, we demonstrate that GLO1 increases anxiety by reducing levels of methylglyoxal (MG), a GABA A receptor agonist. Mice overexpressing Glo1 on a Tg bacterial artificial chromosome displayed increased anxiety-like behavior and reduced brain MG concentrations. Treatment with low doses of MG reduced anxiety-like behavior, while higher doses caused locomotor depression, ataxia, and hypothermia, which are characteristic effects of GABA A receptor activation. Consistent with these data, we found that physiological concentrations of MG selectively activated GABA A receptors in primary neurons. These data indicate that GLO1 increases anxiety by reducing levels of MG, thereby decreasing GABA A receptor activation. More broadly, our findings potentially link metabolic state, neuronal inhibitory tone, and behavior. Finally, we demonstrated that pharmacological inhibition of GLO1 reduced anxiety, suggesting that GLO1 is a possible target for the treatment of anxiety disorders.

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Section: Discussionmentioning

confidence: 90%

Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal

Distler¹,

Plant²,

Sokoloff³

et al. 2012

J. Clin. Invest.

132

214

View full text Add to dashboard Cite

show abstract

“…However there is one study where the diet of autistic children was supplemented with carnosine, with the result that the dipeptide promoted a significant decline in a number of autistic spectrum behavioural symptoms (Chez et al, 2002). Although the underlying mechanism of these effects has not been investigated, it is possible that carnosine's reactivity towards MG might be involved because it has been found that variation in glyoxalase-1 activity seems to affect autistic behaviour (Barua et al, 2011;Junaid et al, 2004) and mood (Fujimoto et al, 2008). It should be pointed out that some of these claims have been disputed (Rehnstrom et al, 2008;Wu et al, 2008).…”

Section: Diet and Control Of Proteotoxicitymentioning

confidence: 99%

Energy metabolism, proteotoxic stress and age-related dysfunction – Protection by carnosine

Hipkiss

2011

Molecular Aspects of Medicine

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“…The broad spatial and temporal expression patterns highlight the crucial importance of the glyoxalase system for biological function. Recent studies revealed alterations in GLO1 expression in neuropsychiatric disorders for mood (Fujimoto et al, 2008), anxiety (Distler et al, 2012;Hovatta et al, 2005;Kromer et al, 2005;Politi et al, 2006) and schizophrenia (Itokawa et al, 2014), but their expression levels have not been examined in postmortem brains. Our analysis, however, did not observe any differences in expression levels of both genes between schizophrenia and controls in BA46 and the hippocampal CA1 subfield.…”

Section: Discussionmentioning

confidence: 99%