Choroid plexus: Target for polypeptides and site of their synthesis

Abstract

Choroid plexus (CP) is an important target organ for polypeptides. The fenestrated phenotype of choroidal endothelium facilitates the penetration of blood‐borne polypeptides across the capillary walls. Thus, both circulating and cerebrospinal fluid (CSF)‐borne polypeptides can reach their receptors on choroidal epithelium. Several polypeptides have been demonstrated to regulate CSF formation by controlling blood flow to choroid plexus and/or the activity of ion transport in choroidal epithelium. However, many ligand‐receptor interactions occurring in the CP are not involved in the regulation of fluid secretion. Increasing evidence suggests that the choroidal epithelium plays an important role in hormonal signaling via a receptor‐mediated transport into the brain (e.g., leptin) and helps to clear certain CSF‐borne polypeptides (e.g., soluble amyloid β‐protein). Thus, impaired choroidal transport or insufficient clearance of polypeptides may contribute to pathogenesis of systemic or central nervous system (CNS) disorders, such as obesity or Alzheimer's disease. CP epithelium is not only a target but is also a source of neuropeptides, growth factors, and cytokines in the CNS. These polypeptides following their release into the CSF may exert distal, endocrine‐like effects on target cells in the brain due to bulk flow of this fluid. Distinct temporal patterns of choroidal expression of several polypeptides are observed during brain development and in various CNS disorders, including traumatic brain injury and ischemia. Therefore, it is proposed that the CP plays an integral role not only in normal brain functioning, but also in the recovery from the injury. This review attempts to critically analyze the available data to support the above hypothesis. Microsc. Res. Tech. 52:65–82, 2001. © 2001 Wiley‐Liss, Inc.

Proteomic analysis of multiple primary cilia reveals a novel mode of ciliary development in mammals

“…This result was consistent with the fact that CPECs express a wide array of cell signaling receptors and ligands (Chodobski and Szmydynger-Chodobska, 2001; Narita et al, 2010), and have multiple functions to maintain brain homeostasis, such as the production of CSF (Narita et al, 2010), receptor-mediated material transport across the blood-CSF barrier (Mitchell et al, 2009), and recruit of lymphocytes for immunosurveillance of the central nervous system (Reboldi et al, 2009). Our data support the idea that mature, non-motile CPEC cilia may be involved in such multiple, tissue-specific signaling events.…”

Proteomic analysis of multiple primary cilia reveals a novel mode of ciliary development in mammals

“…This result was consistent with the fact that CPECs express a wide array of cell signaling receptors and ligands (Chodobski and Szmydynger-Chodobska, 2001; Narita et al, 2010), and have multiple functions to maintain brain homeostasis, such as the production of CSF (Narita et al, 2010), receptor-mediated material transport across the blood-CSF barrier (Mitchell et al, 2009), and recruit of lymphocytes for immunosurveillance of the central nervous system (Reboldi et al, 2009). Our data support the idea that mature, non-motile CPEC cilia may be involved in such multiple, tissue-specific signaling events.…”

CSF turnover reshapes biomarker interpretation in neurodegeneration studies

“…These proteins include immune and signalling factors potentially targeted to the CNS. In line with this, leptin and prolactin, two proteins transported from blood to CSF through the CP 1,45 , were among this small group of PC1-downregulated, VVIA-upregulated proteins (Extended Data 8).…”

Transcriptome signature of the adult mouse choroid plexus

“…While semaphorin 3f [2] and Slits 2 and 3 [28,29] were previously described in the developing CP, we described here for the first time the expression of various netrins and ephrins. The present study also adds to previously described growth and trophic factors [30,31], such as insulin-like growth factor II [32], glial cell line-derived neurotrophic factor [33], transforming growth factor alpha [34], fibroblast growth factor 2 [35] and vascular endothelial growth factor [36]. The expression of genes encoding for several members of the FGF family (those with higher expression value being FGF 18, 9 and 3), neuregulin, betacellulin and epiregulin should be highlighted.…”

Proteomic analysis of multiple primary cilia reveals a novel mode of ciliary development in mammals

“…This result was consistent with the fact that CPECs express a wide array of cell signaling receptors and ligands (Chodobski and Szmydynger-Chodobska, 2001; Narita et al, 2010), and have multiple functions to maintain brain homeostasis, such as the production of CSF (Narita et al, 2010), receptor-mediated material transport across the blood-CSF barrier (Mitchell et al, 2009), and recruit of lymphocytes for immunosurveillance of the central nervous system (Reboldi et al, 2009). Our data support the idea that mature, non-motile CPEC cilia may be involved in such multiple, tissue-specific signaling events.…”

CSF turnover reshapes biomarker interpretation in neurodegeneration studies

“…These proteins include immune and signalling factors potentially targeted to the CNS. In line with this, leptin and prolactin, two proteins transported from blood to CSF through the CP 1,45 , were among this small group of PC1-downregulated, VVIA-upregulated proteins (Extended Data 8).…”

Transcriptome signature of the adult mouse choroid plexus

“…While semaphorin 3f [2] and Slits 2 and 3 [28,29] were previously described in the developing CP, we described here for the first time the expression of various netrins and ephrins. The present study also adds to previously described growth and trophic factors [30,31], such as insulin-like growth factor II [32], glial cell line-derived neurotrophic factor [33], transforming growth factor alpha [34], fibroblast growth factor 2 [35] and vascular endothelial growth factor [36]. The expression of genes encoding for several members of the FGF family (those with higher expression value being FGF 18, 9 and 3), neuregulin, betacellulin and epiregulin should be highlighted.…”

Proteomic analysis of multiple primary cilia reveals a novel mode of ciliary development in mammals

“…This result was consistent with the fact that CPECs express a wide array of cell signaling receptors and ligands (Chodobski and Szmydynger-Chodobska, 2001; Narita et al, 2010), and have multiple functions to maintain brain homeostasis, such as the production of CSF (Narita et al, 2010), receptor-mediated material transport across the blood-CSF barrier (Mitchell et al, 2009), and recruit of lymphocytes for immunosurveillance of the central nervous system (Reboldi et al, 2009). Our data support the idea that mature, non-motile CPEC cilia may be involved in such multiple, tissue-specific signaling events.…”

CSF turnover reshapes biomarker interpretation in neurodegeneration studies

“…These proteins include immune and signalling factors potentially targeted to the CNS. In line with this, leptin and prolactin, two proteins transported from blood to CSF through the CP 1,45 , were among this small group of PC1-downregulated, VVIA-upregulated proteins (Extended Data 8).…”

Transcriptome signature of the adult mouse choroid plexus

“…While semaphorin 3f [2] and Slits 2 and 3 [28,29] were previously described in the developing CP, we described here for the first time the expression of various netrins and ephrins. The present study also adds to previously described growth and trophic factors [30,31], such as insulin-like growth factor II [32], glial cell line-derived neurotrophic factor [33], transforming growth factor alpha [34], fibroblast growth factor 2 [35] and vascular endothelial growth factor [36]. The expression of genes encoding for several members of the FGF family (those with higher expression value being FGF 18, 9 and 3), neuregulin, betacellulin and epiregulin should be highlighted.…”