Corre Christina, Friedel Miriam, Vousden Dulcie A, Metcalf Ariane, Spring Shoshana, Qiu Lily R, Lerch Jason P, Palmert Mark R
Division of Endocrinology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.
Mouse Imaging Centre and Program in Neuroscience and Mental Health, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.
Brain Struct Funct. 2016 Mar;221(2):997-1016. doi: 10.1007/s00429-014-0952-0. Epub 2014 Dec 2.
Males and females exhibit several differences in brain structure and function. To examine the basis for these sex differences, we investigated the influences of sex hormones and sex chromosomes on brain structure and function in mice. We used the Four Core Genotype (4CG) mice, which can generate both male and female mice with XX or XY sex chromosome complement, allowing the decoupling of sex chromosomes from hormonal milieu. To examine whole brain structure, high-resolution ex vivo MRI was performed, and to assess differences in cognitive function, mice were trained on a radial arm maze. Voxel-wise and volumetric analyses of MRI data uncovered a striking independence of hormonal versus chromosomal influences in 30 sexually dimorphic brain regions. For example, the bed nucleus of the stria terminalis and the parieto-temporal lobe of the cerebral cortex displayed steroid-dependence while the cerebellar cortex, corpus callosum, and olfactory bulbs were influenced by sex chromosomes. Spatial learning and memory demonstrated strict hormone-dependency with no apparent influence of sex chromosomes. Understanding the influences of chromosomes and hormones on brain structure and function is important for understanding sex differences in brain structure and function, an endeavor that has eventual implications for understanding sex biases observed in the prevalence of psychiatric disorders.
雄性和雌性在大脑结构和功能上表现出若干差异。为了探究这些性别差异的基础，我们研究了性激素和性染色体对小鼠大脑结构和功能的影响。我们使用了四核心基因型（4CG）小鼠，这种小鼠能够产生具有XX或XY性染色体组成的雄性和雌性小鼠，从而使性染色体与激素环境解耦。为了检查全脑结构，我们进行了高分辨率离体磁共振成像（MRI），并且为了评估认知功能的差异，我们在放射状臂迷宫上对小鼠进行了训练。对MRI数据进行的体素级和体积分析揭示了在30个性别二态性脑区中激素影响与染色体影响之间显著的独立性。例如，终纹床核和大脑皮质的颞顶叶表现出类固醇依赖性，而小脑皮质、胼胝体和嗅球则受性染色体影响。空间学习和记忆表现出严格的激素依赖性，而没有明显的性染色体影响。了解染色体和激素对大脑结构和功能的影响对于理解大脑结构和功能中的性别差异很重要，这一努力最终对于理解在精神疾病患病率中观察到的性别偏见具有重要意义。
