PDF(Pubmed)
Abstract：
In vivo neuroimaging studies have established several reproducible volumetric sex differences in the human brain, but the causes of such differences are hard to parse. While mouse models are useful for understanding the cellular and mechanistic bases of sex-specific brain development, there have been no attempts to formally compare human and mouse neuroanatomical sex differences to ascertain how well they translate. Addressing this question would shed critical light on the use of the mouse as a translational model for sex differences in the human brain and provide insights into the degree to which sex differences in brain volume are conserved across mammals. Here, we use structural magnetic resonance imaging to conduct the first comparative neuroimaging study of sex-specific neuroanatomy of the human and mouse brain. In line with previous findings, we observe that in humans, males have significantly larger and more variable total brain volume; these sex differences are not mirrored in mice. After controlling for total brain volume, we observe modest cross-species congruence in the volumetric effect size of sex across 60 homologous regions (r=0.30). This cross-species congruence is greater in the cortex (r=0.33) than non-cortex (r=0.16). By incorporating regional measures of gene expression in both species, we reveal that cortical regions with greater cross-species congruence in volumetric sex differences also show greater cross-species congruence in the expression profile of 2835 homologous genes. This phenomenon differentiates primary sensory regions with high congruence of sex effects and gene expression from limbic cortices where congruence in both these features was weaker between species. These findings help identify aspects of sex-biased brain anatomy present in mice that are retained, lost, or inverted in humans. More broadly, our work provides an empirical basis for targeting mechanistic studies of sex-specific brain development in mice to brain regions that best echo sex-specific brain development in humans.
摘要：
体内神经成像研究已经在人脑中建立了几种可重复的体积性别差异，但这种差异的原因很难解析。虽然小鼠模型对于理解特定性别大脑发育的细胞和机制基础很有用，没有尝试正式比较人类和小鼠的神经解剖学性别差异，以确定它们的翻译程度。解决这个问题将为使用小鼠作为人类大脑性别差异的转化模型提供关键的启示，并提供对哺乳动物大脑体积性别差异保守程度的见解。这里,我们使用结构磁共振成像对人类和小鼠大脑的性别特异性神经解剖学进行了首次比较神经成像研究。根据以前的发现，我们观察到，在人类中，男性的大脑总体积明显更大，变化更大；这些性别差异在小鼠中没有反映出来。在控制大脑总体积后，我们观察到60个同源区域中性别的体积效应大小的适度跨物种一致性（r=0.30）。皮层（r=0.33）的跨物种一致性大于非皮层（r=0.16）。通过在两个物种中纳入基因表达的区域测量，我们发现，在体积性别差异中具有更大的跨物种一致性的皮质区域在2835个同源基因的表达谱中也显示出更大的跨物种一致性。这种现象将性别效应和基因表达高度一致的初级感觉区域与物种之间这两种特征的一致性较弱的边缘皮层区分开来。这些发现有助于确定保留的小鼠中存在性别偏见的大脑解剖结构的各个方面，丢失,或者在人类中倒置。更广泛地说,我们的工作为将小鼠性别特异性脑发育的机制研究定位到最能反映人类性别特异性脑发育的脑区提供了经验基础.
