Abstract
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.
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Acknowledgments
This work was supported by a research grant from The Canadian Institutes of Health Research. Hormonal analysis by the Endocrine Technology and Support Core was supported by the Oregon National Primate Research Center Core Grant P51 OD011092. The authors thank Christine Crossman and Megan Blacquiere for technical assistance.
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The authors declare that they have no conflict of interest.
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All animal studies and procedures were approved by the Toronto Centre for Phenogenomics (TCP) Animal Care Committee (AUP 09-08-0175) in accordance with recommendations of the Canadian Council on Animal Care, the requirements under Animals for Research Act, RSO 1980, and the TCP Committee Policies and Guidelines. The manuscript does not contain clinical studies or patient data.
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J. P. Lerch and M. R. Palmert are supervising authors who contributed equally.
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Corre, C., Friedel, M., Vousden, D.A. et al. Separate effects of sex hormones and sex chromosomes on brain structure and function revealed by high-resolution magnetic resonance imaging and spatial navigation assessment of the Four Core Genotype mouse model. Brain Struct Funct 221, 997–1016 (2016). https://doi.org/10.1007/s00429-014-0952-0
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DOI: https://doi.org/10.1007/s00429-014-0952-0