Reductions in brain kynurenic acid levels, a neuroinhibitory metabolite, improve cognitive function in diverse organisms. Thus, modulation of kynurenic acid levels is thought to have therapeutic potential in a range of brain disorders. Here we report that the steroid 5-androstene 3β, 17β-diol (ADIOL) reduces kynurenic acid levels and promotes associative learning in Caenorhabditis elegans. We identify the molecular mechanisms through which ADIOL links peripheral metabolic pathways to neural mechanisms of learning capacity. Moreover, we show that in aged animals, which normally experience rapid cognitive decline, ADIOL improves learning capacity. The molecular mechanisms that underlie the biosynthesis of ADIOL as well as those through which it promotes kynurenic acid reduction are conserved in mammals. Thus, rather than a minor intermediate in the production of sex steroids, ADIOL is an endogenous hormone that potently regulates learning capacity by causing reductions in neural kynurenic acid levels.

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类固醇激素 ADIOL 通过降低神经犬尿酸水平来促进学习

大脑犬尿酸（一种神经抑制代谢物）水平的降低可以改善多种生物体的认知功能。因此，调节犬尿酸水平被认为对一系列脑部疾病具有治疗潜力。在这里，我们报告类固醇 5-雄烯 3β, 17β-二醇 (ADIOL) 可以降低秀丽隐杆线虫的犬尿酸水平并促进联想学习。我们确定了 ADIOL 将外周代谢途径与学习能力神经机制联系起来的分子机制。此外，我们发现，在通常认知能力快速下降的老年动物中，ADIOL 可以提高学习能力。ADIOL 生物合成的分子机制以及促进犬尿酸还原的分子机制在哺乳动物中是保守的。因此，ADIOL 不是性类固醇生成过程中的次要中间体，而是一种内源性激素，可通过降低神经犬尿酸水平来有效调节学习能力。