2024年10月31日，美国阿拉巴马大学Jeremy H. Herskowitz等研究人员合作在《自然—神经科学》杂志发表论文揭示，跨生物物理尺度的整合识别人脑连接中个体间变异的分子和细胞相关性。

研究人员表示，大脑连接源于跨生物物理尺度的相互作用，涉及分子、细胞、解剖和网络层面。迄今为止，在这些尺度之间的综合分析进展有限。

为了弥补这一空白，研究人员从98个个体的独特队列中收集了生前神经影像学和遗传数据，以及来自额外额前回和下颞回的死后树突棘形态学、蛋白组学和基因表达数据。

通过整合分子和树突棘形态学数据，研究人员识别出数百种蛋白质，这些蛋白质解释了功能连接和结构共变异的个体间差异。这些蛋白质富含于突触结构和功能、能量代谢和RNA加工中。

通过在遗传、分子、亚细胞和组织层面整合数据，研究人员将突触的特定生化变化与大脑区域之间的连接联系起来。这些结果证明了整合来自不同生物物理尺度的数据的可行性，从而提供了对大脑连接更全面的理解。

附：英文原文

Title: Integration across biophysical scales identifies molecular and cellular correlates of person-to-person variability in human brain connectivity

Author: Ng, Bernard, Tasaki, Shinya, Greathouse, Kelsey M., Walker, Courtney K., Zhang, Ada, Covitz, Sydney, Cieslak, Matt, Weber, Audrey J., Adamson, Ashley B., Andrade, Julia P., Poovey, Emily H., Curtis, Kendall A., Muhammad, Hamad M., Seidlitz, Jakob, Satterthwaite, Ted, Bennett, David A., Seyfried, Nicholas T., Vogel, Jacob, Gaiteri, Chris, Herskowitz, Jeremy H.

Issue&Volume: 2024-10-31

Abstract: Brain connectivity arises from interactions across biophysical scales, ranging from molecular to cellular to anatomical to network level. To date, there has been little progress toward integrated analysis across these scales. To bridge this gap, from a unique cohort of 98 individuals, we collected antemortem neuroimaging and genetic data, as well as postmortem dendritic spine morphometric, proteomic and gene expression data from the superior frontal and inferior temporal gyri. Through the integration of the molecular and dendritic spine morphology data, we identified hundreds of proteins that explain interindividual differences in functional connectivity and structural covariation. These proteins are enriched for synaptic structures and functions, energy metabolism and RNA processing. By integrating data at the genetic, molecular, subcellular and tissue levels, we link specific biochemical changes at synapses to connectivity between brain regions. These results demonstrate the feasibility of integrating data from vastly different biophysical scales to provide a more comprehensive understanding of brain connectivity.

DOI: 10.1038/s41593-024-01788-z

Source: https://www.nature.com/articles/s41593-024-01788-z