Polymorphism within a Neuronal Activity-Dependent Enhancer of NgR1 Is Associated with Corpus Callosum Morphology in Humans
Polymorphism within a Neuronal Activity-Dependent Enhancer of NgR1 Is Associated with Corpus Callosum Morphology in Humans
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NgR1 神经元活动依赖性增强子内的多态性与人类胼胝体形态相关
DOI：
10.1159/000430463
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Murai T
中科院分区：
文献类型：
--
作者：
Isobe M;Tanigaki K; Muraki K; Miyata J; Takemura A; Sugihara G;Takahashi H; Aso T; Fukuyama H; Hazama M;Murai T
人类Nogo-66受体1 （NgR1）基因，也被称为Nogo受体1或网状4受体（RTN4R），位于22q11中。2、抑制轴突生长和突触可塑性。22q11的患者。2缺失综合征表现为大脑形态的多种改变，胼胝体（CC）异常是最突出和最常报道的。因此，我们假设，在人类中，NgR1可能参与CC的形成。我们重点研究了与精神分裂症相关的NgR1的单核苷酸多态性rs701428。我们利用磁共振成像技术研究了rs701428基因型对50名健康受试者CC结构的影响。rs701428多态性与健康受试者CC结构变异相关；与主要等位基因纯合的参与者相比，次要A等位基因携带者的CC整体体积更大，CC中心区域的径向扩散率更低。此外，我们发现含有rs701428的NgR1 3 '区是神经元活性依赖的增强子，并且rs701428的次要等位基因a易受MYBL2对增强子活性的调控。我们的研究结果表明，NgR1可以影响人类大脑白质的宏观和微观结构。
The human Nogo-66 receptor 1 (NgR1) gene, also termed Nogo receptor 1 or reticulon 4 receptor (RTN4R) and located within 22q11. 2, inhibits axonal growth and synaptic plasticity. Patients with the 22q11. 2 deletion syndrome show multiple changes in brain morphology, with corpus callosum (CC) abnormalities being among the most prominent and frequently reported. Thus, we hypothesized that, in humans, NgR1 may be involved in CC formation. We focused on rs701428, a single nucleotide polymorphism of NgR1, which is associated with schizophrenia. We investigated the effects of the rs701428 genotype on CC structure in 50 healthy participants using magnetic resonance imaging. Polymorphism of rs701428 was associated with CC structural variation in healthy participants; specifically, minor A allele carriers had larger whole CC volumes and lower radial diffusivity in the central CC region compared with major G allele homozygous participants. Furthermore, we showed that the NgR1 3′ region, which contains rs701428, is a neuronal activity-dependent enhancer, and that the minor A allele of rs701428 is susceptible to regulation of enhancer activity by MYBL2. Our results suggest that NgR1 can influence the macro-and microstructure of the white matter of the human brain.