title: 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.
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.
authors.affiliation: Division of Endocrinology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. christina.corre@sickkids.ca.
authors.forename: Christina
authors.initials: C
authors.lastname: Corre
authors.affiliation: Mouse Imaging Centre and Program in Neuroscience and Mental Health, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.
authors.forename: Miriam
authors.initials: M
authors.lastname: Friedel
authors.affiliation: Mouse Imaging Centre and Program in Neuroscience and Mental Health, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.|Department of Medical Biophysics, The University of Toronto, Toronto, ON, Canada.
authors.forename: Dulcie A
authors.initials: DA
authors.lastname: Vousden
authors.affiliation: Mouse Imaging Centre and Program in Neuroscience and Mental Health, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.
authors.forename: Ariane
authors.initials: A
authors.lastname: Metcalf
authors.affiliation: Mouse Imaging Centre and Program in Neuroscience and Mental Health, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.
authors.forename: Shoshana
authors.initials: S
authors.lastname: Spring
authors.affiliation: Division of Endocrinology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada.|Institute of Medical Science, The University of Toronto, Toronto, ON, Canada.
authors.forename: Lily R
authors.initials: LR
authors.lastname: Qiu
authors.affiliation: Mouse Imaging Centre and Program in Neuroscience and Mental Health, The Hospital for Sick Children, 25 Orde Street, Toronto, ON, M5T 3H7, Canada.|Department of Medical Biophysics, The University of Toronto, Toronto, ON, Canada.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Lerch
authors.affiliation: Division of Endocrinology, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada. mark.palmert@sickkids.ca.|Institute of Medical Science, The University of Toronto, Toronto, ON, Canada. mark.palmert@sickkids.ca.|Departments of Paediatrics and Physiology, The University of Toronto, Toronto, ON, Canada. mark.palmert@sickkids.ca.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Palmert
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D012739:Gonadal Steroid Hormones / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D012727:Sex Characteristics; D012730:Sex Chromosomes / Q000502:physiology*; D012737:Sex Factors; D065854:Spatial Navigation
chemical_list: D012739:Gonadal Steroid Hormones
keywords: Brain structure; Cognition; Four Core Genotype Mice; Sex chromosomes; Sex differences; Sex hormones