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【编译】7 -羟基孕甾酮作为神经元激动剂通过多

现在人们逐渐了解，在脑内及其它神经系统中可以不断分泌类固醇，这种类固醇称为神经类固醇，而且它可以从储存在脊椎动物脑内的胆固醇中转化而来。在该研究中，我们在蝾螈脑内发现一种以前人们从未介绍过的两栖动物神经类固醇物质－7 -羟基孕甾酮，这种物质可以促进蝾螈的活动能力。我们通过生化手段以及与其它多技术联用的分析方法（如：高效液相色谱、薄层色谱和气质联用）确定了在蝾螈脑内广泛存在一种神经类固醇－7 -羟基孕甾酮。我们发现从中脑和后脑中分泌7 -羟基孕甾酮的量要高于从端脑和外周类固醇分泌腺中的分泌量，另外，7 -羟基孕甾酮在蝾螈脑内的含量随着每年其繁殖周期而呈现显著的变化，其峰值出现在春季，而春季也是蝾螈活动力最强的时候。在对非繁殖期的蝾螈进行行为学测试中，我们发现这种早期未报道的两栖类动物神经类固醇确实能增强动物的活动能力。进一步的体外实验结果表明，给予7 -羟基孕甾酮后，在培养的非繁殖期的蝾螈脑组织中分泌的多巴胺与7 -羟基孕甾酮呈现出剂量的依赖性关系，而且多巴胺D2样受体拮抗剂可以削弱7 -羟基孕甾酮对蝾螈的促活动力作用。以上结果均表明，7 -羟基孕甾酮作为一种神经元激动剂可以通过多巴胺能神经元系统促进繁殖期蝾螈的活动能力。该研究说明了7 -羟基孕甾酮在脊椎动物体内的生理作用；与此同时，该研究也从另一个角度支持了关于“运动行为控制机制”的发现。

7 -Hydroxypregnenolone acts as a neuronal activator to stimulate locomotor activity of breeding newts by means of the dopaminergic system
It is becoming clear that steroids can be synthesized de novo by the brain and other nervous systems. Such steroids are called neurosteroids, and de novo neurosteroidogenesis from cholesterol is a conserved property of vertebrate brains. In this study, we show that the newt brain actively produces 7 -hydroxypregnenolone, a previously undescribed amphibian neurosteroid that stimulates locomotor activity. 7 -hydroxypregnenolone was identified as a most abundant amphibian neurosteroid in the newt brain by using biochemical techniques combined with HPLC, TLC, and GC-MS analyses. The production of 7 -hydroxypregnenolone in the diencephalon and rhombencephalon was higher than that in the telencephalon and peripheral steroidogenic glands. In addition, 7 -hydroxypregnenolone synthesis in the brain showed marked changes during the annual breeding cycle, with a maximal level in the spring breeding period when locomotor activity of the newt increases. Behavioral analysis of newts in the nonbreeding period demonstrated that administration of this previously undescribed amphibian neurosteroid acutely increased locomotor activity. In vitro analysis further revealed that 7 -hydroxypregnenolone treatment resulted in a dose-dependent increase in the release of dopamine from cultured brain tissue of nonbreeding newts. The effect of this neurosteroid on locomotion also was abolished by dopamine D2-like receptor antagonists. These results indicate that 7 -hydroxypregnenolone acts as a neuronal activator to stimulate locomotor activity of breeding newts through the dopaminergic system. This study demonstrates a physiological function of 7 -hydroxypregnenolone that has not been described previously in any vertebrate class. This study also provides findings on the regulatory mechanism of locomotor activity from a unique standpoint.

http://www.pnas.org/cgi/reprint/101/49/17282.pdf [标签:content1][标签:content2]

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作者:admin@医学,生命科学    2011-08-14 05:14
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