JCI：焦虑症基因GLO1可能成为治疗靶标

芝加哥大学的研究人员已经找到了一个与焦虑症有关的基因，该基因编码乙二醛酶I （GLO1）。然而该基因与焦虑症之间关联的机制目前尚不清楚。

在美国最普遍的精神疾病是焦虑症其中包括创伤后应激障碍、社交恐怖症等。

利用小鼠模型， Margaret Distler和她的团队想确定是否GlO1的早期底物--甲基乙二醛能否对神经系统有影响。

GLO1的正常作用是降低糖酵解的毒副产物，但糖酵解的毒副产物与焦虑之间的关联还不甚明了。

研究人员发现，甲基乙二醛能刺激GABAA受体。目前，以 GABAA受体的药物或许可以作为焦虑治疗的药物。这项研究确切证实了焦虑与GLO1之间确实有联系。

此外，该研究小组发现防止抑制GLO1能改善小鼠的焦虑行为，表明GLO1可能是一个潜的治疗靶标。据研究人员表示这项研究结果不仅为焦虑症，也为其他与GLO1相关的神经系统疾病包括精神分裂症、情感性精神障碍以及自闭症等带来了新的治疗方法。

doi:10.1172/JCI61319
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Glyoxalase 1 increases anxiety by reducing GABAA receptor agonist methylglyoxal

Margaret G. Distler¹, Leigh D. Plant^2,3, Greta Sokoloff⁴, Andrew J. Hawk¹, Ivy Aneas⁴, Gerald E. Wuenschell⁵, John Termini⁵, Stephen C. Meredith^1,6, Marcelo A. Nobrega⁴ and Abraham A. Palmer^4,7

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.