Comparative neuroimaging of sex differences in human and mouse brain anatomy
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 bee...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2024-03-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/92200 |
| _version_ | 1797260781912326144 |
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| author | Elisa Guma Antoine Beauchamp Siyuan Liu Elizabeth Levitis Jacob Ellegood Linh Pham Rogier B Mars Armin Raznahan Jason P Lerch |
| author_facet | Elisa Guma Antoine Beauchamp Siyuan Liu Elizabeth Levitis Jacob Ellegood Linh Pham Rogier B Mars Armin Raznahan Jason P Lerch |
| author_sort | Elisa Guma |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T23:30:47Z |
| format | Article |
| id | doaj.art-d7000913fd3948719eb239645e706653 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-24T23:30:47Z |
| publishDate | 2024-03-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-d7000913fd3948719eb239645e7066532024-03-15T15:09:03ZengeLife Sciences Publications LtdeLife2050-084X2024-03-011310.7554/eLife.92200Comparative neuroimaging of sex differences in human and mouse brain anatomyElisa Guma0https://orcid.org/0000-0003-4651-8529Antoine Beauchamp1Siyuan Liu2https://orcid.org/0000-0003-3661-6248Elizabeth Levitis3Jacob Ellegood4Linh Pham5Rogier B Mars6Armin Raznahan7https://orcid.org/0000-0002-5622-1190Jason P Lerch8Section on Developmental Neurogenomics, Human Genetics Branch, National Institute of Mental Health, Bethesda, United StatesMouse Imaging Centre, Toronto, Canada; The Hospital for Sick Children, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, CanadaSection on Developmental Neurogenomics, Human Genetics Branch, National Institute of Mental Health, Bethesda, United StatesSection on Developmental Neurogenomics, Human Genetics Branch, National Institute of Mental Health, Bethesda, United StatesMouse Imaging Centre, Toronto, Canada; The Hospital for Sick Children, Toronto, CanadaSection on Developmental Neurogenomics, Human Genetics Branch, National Institute of Mental Health, Bethesda, United States; Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical 15 Neurosciences, University of Oxford, Oxford, United KingdomWellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical 15 Neurosciences, University of Oxford, Oxford, United Kingdom; Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, NetherlandsSection on Developmental Neurogenomics, Human Genetics Branch, National Institute of Mental Health, Bethesda, United StatesMouse Imaging Centre, Toronto, Canada; The Hospital for Sick Children, Toronto, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Canada; Wellcome Centre for Integrative Neuroimaging, Nuffield Department of Clinical 15 Neurosciences, University of Oxford, Oxford, United KingdomIn 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.https://elifesciences.org/articles/92200sex differencesneuroimagingcomparative anatomytranslational neurosciencespatial transcriptomics |
| spellingShingle | Elisa Guma Antoine Beauchamp Siyuan Liu Elizabeth Levitis Jacob Ellegood Linh Pham Rogier B Mars Armin Raznahan Jason P Lerch Comparative neuroimaging of sex differences in human and mouse brain anatomy eLife sex differences neuroimaging comparative anatomy translational neuroscience spatial transcriptomics |
| title | Comparative neuroimaging of sex differences in human and mouse brain anatomy |
| title_full | Comparative neuroimaging of sex differences in human and mouse brain anatomy |
| title_fullStr | Comparative neuroimaging of sex differences in human and mouse brain anatomy |
| title_full_unstemmed | Comparative neuroimaging of sex differences in human and mouse brain anatomy |
| title_short | Comparative neuroimaging of sex differences in human and mouse brain anatomy |
| title_sort | comparative neuroimaging of sex differences in human and mouse brain anatomy |
| topic | sex differences neuroimaging comparative anatomy translational neuroscience spatial transcriptomics |
| url | https://elifesciences.org/articles/92200 |
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