Research Centre Jülich, Institute of Neuroscience and Medicine (INM-1), 52425, Jülich, Germany.
Department of Biomedicine, University of Basel, 4031, Basel, Switzerland.
Brain Struct Funct. 2018 Jun;223(5):2335-2342. doi: 10.1007/s00429-018-1620-6. Epub 2018 Feb 24.
Decoding the chain from genes to cognition requires detailed insights how areas with specific gene activities and microanatomical architectures contribute to brain function and dysfunction. The Allen Human Brain Atlas contains regional gene expression data, while the JuBrain Atlas offers three-dimensional cytoarchitectonic maps reflecting interindividual variability. To date, an integrated framework that combines the analytical benefits of both scientific platforms towards a multi-level brain atlas of adult humans was not available. We have, therefore, developed JuGEx, a new method for integrating tissue transcriptome and cytoarchitectonic segregation. We investigated differential gene expression in two JuBrain areas of the frontal pole that we have structurally and functionally characterized in previous studies. Our results show a significant upregulation of MAOA and TAC1 in the medial area frontopolaris which is a node in the limbic-cortical network and known to be susceptible for gray matter loss and behavioral dysfunction in patients with depression. The MAOA gene encodes an enzyme which is involved in the catabolism of dopamine, norepinephrine, serotonin, and other monoaminergic neurotransmitters. The TAC1 locus generates hormones that play a role in neuron excitations and behavioral responses. Overall, JuGEx provides a new tool for the scientific community that empowers research from basic, cognitive and clinical neuroscience in brain regions and disease models with regard to gene expression.
从基因到认知的解码需要详细了解具有特定基因活性和微观解剖结构的区域如何促进大脑功能和功能障碍。Allen 人类大脑图谱包含区域基因表达数据，而 JuBrain 图谱提供反映个体间变异性的三维细胞构筑图。迄今为止，还没有一个整合这两个科学平台的分析优势的综合框架来构建成人多层面大脑图谱。因此，我们开发了 JuGEx，这是一种用于整合组织转录组和细胞构筑分隔的新方法。我们研究了我们在之前的研究中从结构和功能上进行了表征的额叶极的两个 JuBrain 区域中的差异基因表达。我们的结果显示，内侧额极区的 MAOA 和 TAC1 显著上调，该区域是边缘皮质网络的一个节点，已知易患抑郁症患者的灰质损失和行为功能障碍。MAOA 基因编码一种参与多巴胺、去甲肾上腺素、血清素和其他单胺能神经递质代谢的酶。TAC1 基因座产生的激素在神经元兴奋和行为反应中发挥作用。总的来说，JuGEx 为科学界提供了一个新工具，使研究人员能够在与基因表达相关的大脑区域和疾病模型中进行基础、认知和临床神经科学研究。
