Abstract

Cerebrospinal fluid (CSF) is the liquid that fills the brain ventricles. CSF represents not only a mechanical brain protection but also a rich source of signalling factors modulating diverse processes during brain development and adulthood. The choroid plexus (CP) is a major source of CSF and as such it has recently emerged as an important mediator of extracellular signalling within the brain. Growing interest in the CP revealed its capacity to release a broad variety of bioactive molecules that, via CSF, regulate processes across the whole central nervous system (CNS). Moreover, CP has been also recognized as a sensor, responding to altered composition of CSF associated with changes in the patterns of CNS activity. In this review, we summarize the recent advances in our understanding of the CP as a signalling centre that mediates long-range communication in the CNS. By providing a detailed account of the CP secretory repertoire, we describe how the CP contributes to the regulation of the extracellular environment—in the context of both the embryonal as well as the adult CNS. We highlight the role of the CP as an important regulator of CNS function that acts via CSF-mediated signalling. Further studies of CP–CSF signalling hold the potential to provide key insights into the biology of the CNS, with implications for better understanding and treatment of neuropathological conditions.

Highlights

  • A singular feature of the central nervous system (CNS), crucial to its function following neural tube closure and homeostasis throughout adulthood, is the presence ofCSF, which represents the key signalling interface between various distant regions of the CNS

  • Cerebrospinal fluid (CSF) has been assumed to primarily act as a fluid cushion providing mechanistic protection to the brain, an osmotic buffer system, and a route for clearance of metabolic waste and toxic compounds from the brain. This rather narrow view has been recently challenged by the growing evidence pointing to the expanded role of CSF as a conduit for delivery of instructive cues involved in the regulation of multiple aspects of CNS embryogenesis, adult neurogenesis, and modulation of adult brain function [4]

  • The choroid plexus (CP) is a secretory tissue protruding into the lumen of all brain ventricles, namely the lateral ventricle CP (LV CP), the 3rd ventricle CP, and 4th ventricle CP (4V CP), in the form of a sheet of epithelial cells that are in direct contact with the CSF and encapsulate richly-vascularized stroma [22]

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Summary

Introduction

A singular feature of the CNS, crucial to its function following neural tube closure and homeostasis throughout adulthood, is the presence ofCSF, which represents the key signalling interface between various distant regions of the CNS. CSF has been assumed to primarily act as a fluid cushion providing mechanistic protection to the brain, an osmotic buffer system, and a route for clearance of metabolic waste and toxic compounds from the brain This rather narrow view has been recently challenged by the growing evidence pointing to the expanded role of CSF as a conduit for delivery of instructive cues involved in the regulation of multiple aspects of CNS embryogenesis, adult neurogenesis, and modulation of adult brain function [4]. We aim to provide an overview of recent advances regarding the composition of CSF from the standpoint of CP secretome and its multifaceted impact on the regulation of various aspects of CNS embryogenesis and maintenance in adulthood

CSF—An Intrinsic Component of CNS Environment
The Choroid Plexus—Key Regulator of CSF Production
The CP–CSF Signalling Axis and Its Key Mediators
Exosomes in CP–CSF Signalling
Lipoprotein Complexes in CP–CSF Signalling
The Target Brain Regions of CP–CSF Signalling
Findings
Concluding Remarks
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