University of Wuerzburg, Department of Psychiatry, Psychosomatics and Psychotherapy, Wuerzburg, Germany.
Neuroimage. 2011 Aug 15;57(4):1617-23. doi: 10.1016/j.neuroimage.2011.05.034. Epub 2011 May 17.
Nitric oxide (NO) synthase produces NO, which serves as first and second messenger in neurons, where the protein is encoded by the NOS1 gene. A functional variable number of tandem repeats (VNTR) polymorphism in the promoter region of the alternative first exon 1f of NOS1 is associated with various functions of human behavior, for example increased impulsivity, while another, non-functional variant was linked to decreased verbal working memory and a heightened risk for schizophrenia. We therefore investigated the influence of NOS1 ex 1f-VNTR on working memory function as reflected by both behavioral measures and prefrontal oxygenation. We hypothesized that homozygous short allele carriers exhibit altered brain oxygenation in task-related areas, namely the dorsolateral and ventrolateral prefrontal cortex and the parietal cortex. To this end, 56 healthy subjects were stratified into a homozygous long allele group and a homozygous short allele group comparable for age, sex and intelligence. All subjects completed a letter n-back task (one-, two-, and three-back), while concentration changes of oxygenated (O(2)Hb) hemoglobin in the prefrontal cortex were measured with functional near-infrared spectroscopy (fNIRS). We found load-associated O(2)Hb increases in the prefrontal and parts of the parietal cortex. Significant load-associated oxygenation differences between the two genotype groups could be shown for the dorsolateral prefrontal cortex and the parietal cortex. Specifically, short allele carriers showed a significantly larger increase in oxygenation in all three n-back tasks. This suggests a potential compensatory mechanism, with task-related brain regions being more active in short allele carriers to compensate for reduced NOS1 expression.
一氧化氮合酶（NOS）产生一氧化氮（NO），作为神经元中的第一信使和第二信使，其蛋白由 NOS1 基因编码。NOS1 基因的第一个外显子 1f 的启动子区域存在一个功能性的串联重复数可变（VNTR）多态性，与人类行为的各种功能有关，例如冲动性增加，而另一个非功能性的变体与言语工作记忆减少和精神分裂症风险增加有关。因此，我们研究了 NOS1 ex 1f-VNTR 对工作记忆功能的影响，这种影响通过行为测量和前额叶氧合作用来反映。我们假设纯合短等位基因携带者在与任务相关的区域（即背外侧和腹外侧前额叶皮层以及顶叶皮层）中表现出改变的脑氧合。为此，我们将 56 名健康受试者分为纯合长等位基因组和纯合短等位基因组，两组在年龄、性别和智力方面具有可比性。所有受试者均完成字母 n 回任务（1 回、2 回和 3 回），同时通过功能近红外光谱（fNIRS）测量前额叶皮层中含氧（O2Hb）血红蛋白的浓度变化。我们发现前额叶皮层和部分顶叶皮层的氧合作用与负荷相关增加。在两个基因型组之间可以观察到与负荷相关的氧合作用差异，特别是在背外侧前额叶皮层和顶叶皮层。具体来说，短等位基因携带者在所有三个 n 回任务中都表现出明显更大的氧合作用增加。这表明存在一种潜在的补偿机制，短等位基因携带者的与任务相关的大脑区域更加活跃，以补偿 NOS1 表达的减少。
