Abstract
Sex differences exist in behaviors, disease and neuropsychiatric disorders. Sexual dimorphisms however, have yet to be studied across the whole brain and across a comprehensive time course of postnatal development. Here, we use manganese-enhanced MRI (MEMRI) to longitudinally image male and female C57BL/6J mice across 9 time points, beginning at postnatal day 3. We recapitulate findings on canonically dimorphic areas, demonstrating MEMRI’s ability to study neuroanatomical sex differences. We discover, upon whole-brain volume correction, that neuroanatomical regions larger in males develop earlier than those larger in females. Groups of areas with shared sexually dimorphic developmental trajectories reflect behavioral and functional networks, and expression of genes involved with sex processes. Also, post-pubertal neuroanatomy is highly individualized, and individualization occurs earlier in males. Our results demonstrate the ability of MEMRI to reveal comprehensive developmental differences between male and female brains, which will improve our understanding of sex-specific predispositions to various neuropsychiatric disorders.
Highlights
Sex differences exist in behaviors, disease and neuropsychiatric disorders
The putamen, globus pallidus, basal ganglia, amygdala and hypothalamus are larger in males, while the caudate, thalamus and hippocampus are larger in females[10,11,12,13]
manganese-enhanced MRI (MEMRI) captures neurodevelopment without adverse effects
Summary
Sex differences exist in behaviors, disease and neuropsychiatric disorders. Sexual dimorphisms have yet to be studied across the whole brain and across a comprehensive time course of postnatal development. Females tend to have a predisposition for disorders that have later onset, during adolescence and early adulthood, which include major depressive disorders, anxiety disorders and eating disorders[4] Key to understanding these sex-specific vulnerabilities and predispositions is a better understanding of the normal development of sex differences in the brain. Noninvasive image acquisition using MRI enables repeated scanning of the same individual to study longitudinal development This is important because of the temporal nature of sex differences in the brain[5], behaviors, and risk factors for psychiatric disorders. The putamen, globus pallidus, basal ganglia, amygdala and hypothalamus are larger in males, while the caudate, thalamus and hippocampus are larger in females[10,11,12,13] Many of these sex differences arise during a critical period of sexual differentiation that occurs during neonatal life. Sex chromosomes themselves influence sex differences in brain anatomy[16]
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