Sex differences in the lateral ventricle choroid plexus

The cerebrospinal fluid (CSF) flows through the ventricles of the brain and plays an important role in the transport of nutrients and signalling molecules throughout the ventricular system. CSF composition is dynamic and changes with ageing, but also in different physiological states. The choroid plexus (ChP) produces CSF and by physically separating the CSF from the circulation, forms the blood-CSF barrier. As a central hub with multiple functions, the ChP is emerging as a key contributor to normal brain physiology and disease. Despite its important role in brain function, sex differences in the ChP remain poorly understood. Here we investigate sex differences in the lateral ventricle choroid plexus (LVChP) at the anatomical, cellular and molecular levels. Our comparison of the male and female LVChP transcriptome revealed marked sex differences in various aspects of LVChP functions. Furthermore, cell type analysis of differentially expressed genes in male and female LVChP revealed a prevalence of macrophage-associated genes in the female LVChP. Quantification of LVChP macrophages in vivo revealed enrichment of different subpopulations in males and females, with an overall higher number of macrophages in females. In addition, male and female LVChP-secreted factors had different effects on FACS-purified male and female adult neural stem cells in vitro. Taken together, these results show that male and female LVChP differ at cellular, transcriptomic and secretory levels, suggesting differences in their function and differential regulation of adult neural stem cells of the ventricular-subventricular zone (V-SVZ). Finally, the establishment of a dissociation method to obtain single viable LVChP cells opens the way for further ongoing analyses, including single cell RNAseq profiling of adult male and female LVChP, which will shed light on further cell type-specific sex differences in gene expression and function. These findings contribute to a better understanding of sex differences in the LVChP at the cellular and molecular level. Further research in this field will provide insights into the underlying processes and functional relevance of sex differences in the LVChP, which in turn may drive the development of sex-specific therapeutic strategies in clinical settings.