Hypercholesterolemia negatively influences morphology and molecular markers of epithelial cells within the choroid plexus in rabbits

Fumiko Obata,Keishi Narita

doi:10.1186/s12987-020-0175-0

Abstract

BackgroundChoroid plexus (CP) is an important tissue not only to produce cerebrospinal fluid (CSF) but also to regulate substances that are secreted into or absorbed from CSF through blood–cerebrospinal fluid barrier (BCSFB) formed by CP epithelial cells (CPECs). CPECs display signs of deterioration in aged and diseased people. However, whether CPECs in hypercholesterolemic animals develop such damage is not known.MethodsWe used cholesterol-fed wild-type or Watanabe hereditary hyperlipidemic (WHHL) rabbits of identical age to determine CPEC changes in terms of morphology and protein expression/localization.ResultsCompared with non-cholesterol-fed control rabbits, prolonged exposure to cholesterol reduced CPEC height and increased lipofuscin levels in CPECs, indicating cellular damage. Expression of aquaporin 1 on the apical membranes of CPECs was diminished in cholesterol-exposed rabbits, implying a reduced CSF-producing function in the CP. The rabbit macrophage-specific antibody (RAM11) immunoreaction became positive in CPECs adjacent to foam cells, indicating an alteration in this cell type.ConclusionCholesterol insults from the circulation (which is reflected by foam-cell accumulation in the CP) induce CPEC dysfunction, and the latter seems to be enhanced by foam cells in hypercholesterolemic rabbits.

Highlights

Choroid plexus (CP) is an important tissue to produce cerebrospinal fluid (CSF) and to regulate substances that are secreted into or absorbed from CSF through blood–cerebrospinal fluid barrier (BCSFB) formed by CP epithelial cells (CPECs)
The other model was spontaneous hypercholesterolemia of 32-week-old Watanabe hereditary hyperlipidemic (WHHL) rabbits. This spontaneously hyperlipidemic strain carries a genetic mutation in the low-density lipoprotein receptor (LDLR) that slows down the transport of the LDLR to the hepatocyte surface
We showed that signs of damage were evident in the CPECs of hyperlipidemic rabbits

Summary

Introduction

Choroid plexus (CP) is an important tissue to produce cerebrospinal fluid (CSF) and to regulate substances that are secreted into or absorbed from CSF through blood–cerebrospinal fluid barrier (BCSFB) formed by CP epithelial cells (CPECs). The choroid plexus (CP) is a secretory and scavenging tissue in ventricles of the brain It has important functions in brain development and homeostasis [1, 2]. While producing the cerebrospinal fluid (CSF) into the brain ventricles, CPECs form a tight junction known as the blood–cerebrospinal fluid barrier (BCSFB) to allow only selective substances (ions, amino acids, folate, glucose, transthyretin, vitamins B6, B12, C and E) to traffic between the systemic circulation and the CSF [1,2,3,4]. CPECs transport proteins such as WNT5A via lipoproteins as vehicles into CSF [10, 11]

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