Abstract
The choroid plexus and cerebral ventricles are critical structures for the production of cerebral spinal fluid (CSF) and play an important role in regulating ion and metal transport in the brain, however many aspects of its roles in normal physiology and disease states, such as psychiatric illness, remain unknown. The choroid plexus is difficult to examine in vivo, and in situ ex vivo, and as such has typically been examined indirectly with radiolabeled tracers or ex vivo stains, making measurements of the endogenous K+, Cl−, and Ca+ distributions unreliable. In the present study, we directly examined the distribution of endogenous ions and biologically relevant transition metals in the choroid plexus and regions surrounding the ventricles (ventricle wall, cortex, corpus callosum, striatum) using X-ray fluorescence imaging (XFI). We find that the choroid plexus was rich in Cl− and Fe while K+ levels increase further from the ventricle as Cl− levels decrease, consistent with the known role of ion transporters in the choroid plexus CSF production. A polyI:C offspring displayed enlarged ventricles, elevated Cl− surrounding the ventricles, and intraventricular calcifications. These observations fit with clinical findings in patients with schizophrenia and suggest maternal treatment with polyI:C may lead to dysfunctional ion regulation in offspring. This study demonstrates the power of XFI for examining the endogenous elemental distributions of the ventricular system in healthy brain tissue as well as disease models.
Highlights
The choroid plexus is the main cellular structure within the ventricular system, and has long been considered a filter or “kidney of the brain”
To further demonstrate the potential of incorporating X-ray fluorescence imaging (XFI) in future studies to correlate altered choroid plexus function with altered brain ion homeostasis in neurological disease or disorders, we report a case study highlighting the elemental alterations that may occur within the choroid plexus and ventricular system in an animal model of schizophrenia, which is characterized by altered brain serotonin homeostasis and enlarged ventricles
Cl−and K+ were observed in high concentration within the choroid plexus epithelium, K+ was observed in relatively low concentration outside of the epithelium, while Cl− was still abundant (Fig 2)
Summary
The choroid plexus is the main cellular structure within the ventricular system, and has long been considered a filter or “kidney of the brain”. Despite a relatively simple cellular composition, the chemical and physiological roles of the choroid plexus are not fully known. X-Ray Fluorescence Imaging of Ions Surrounding Brain Ventricles and a postdoctoral fellow funded by the joint Canadian Institutes of Health Research (CIHR)/Heart and Stroke Foundation of Canada (HSFC) Synchrotron Medical Imaging Team Grant #CIF 99472. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript
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