Reelin expression in brain endothelial cells: an electron microscopy study.

Emma Perez-Costas,Erin Y Fenton,Hector J Caruncho

doi:10.1186/s12868-015-0156-4

Emma Perez-Costas, Erin Y Fenton + Show 1 more

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https://doi.org/10.1186/s12868-015-0156-4

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Abstract

BackgroundReelin expression and function have been extensively studied in the brain, although its expression has been also reported in other tissues including blood. This raises the possibility that reelin might be able to cross the blood-brain barrier, which could be functionally relevant. Up-to-date no studies have been conducted to assess if reelin is present in the blood-brain barrier, which is mainly constituted by tightly packed endothelial cells. In this report we assessed the expression of reelin in brain capillaries using immunocytochemistry and electron microscopy.ResultsAt the light microscope, reelin immunolabeling appeared in specific endothelial cells in brain areas that presented abundant diffuse labeling for this protein (e.g., layer I of the cortex, or the stratum lacunosum moleculare of the hippocampus), while it was mostly absent from capillaries in other brain areas (e.g., deeper cortical layers, or the CA1 layer of the hippocampus). As expected, at the electron microscope reelin labeling was observed in neurons of the cortex, where most of the labeling was associated with the rough endoplasmic reticulum. Importantly, reelin was also observed in some endothelial cells located in small capillaries, which confirmed the findings obtained at the light microscope. In these cells, reelin labeling was located primarily in caveolae (i.e., vesicles of transcytosis), and associated with the plasma membrane of the luminal side of endothelial cells. In addition, some scarce labeling was observed in the nuclear membrane.ConclusionsThe presence of reelin immunolabeling in brain endothelial cells, and particularly in caveolar vesicles within these cells, suggests that reelin and/or reelin peptides may be able to cross the blood-brain barrier, which could have important physiological, pathological, and therapeutic implications.

Highlights

Reelin expression and function have been extensively studied in the brain, its expression has been reported in other tissues including blood
As shown in previous studies [6,7,8,9,13,34,35], at the light microscope the most intense reelin labeling was observed in layer I of the cortex and in the stratum lacunosum moleculare of the hippocampus, where neuronal and diffuse labeling were observed (Figure 1)
This suggests that a possible secretion and/or transport of reelin by endothelial cells may take place primarily in areas of heavy diffuse reelin staining [see reference 32]

Summary

Introduction

Reelin expression and function have been extensively studied in the brain, its expression has been reported in other tissues including blood. Reelin is a large extracellular matrix glycoprotein, which was originally discovered in the mouse brain [1] This protein is secreted by Cajal-Retzius cells during brain development, regulating neural migration and dendritic spine maturation (see as reviews [2,3,4,5]). Some ultrastructural studies have focused primarily on the subcellular expression of reelin in neurons and neuropil within the CNS, where immunolabeling has been reported in the rough endoplasmic reticulum, axons, Perez-Costas et al BMC Neuroscience (2015) 16:16 dendritic spines, and in the extracellular matrix [31,32,33,34,35]. In order to assess these possibilities we undertook an electron microscopy study of reelin immunolabeling in brain endothelial cells

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