title: Reelin expression in brain endothelial cells: an electron microscopy study.
abstract: BACKGROUND
  Reelin 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.
  
  
  RESULTS
  At 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Psychology, University of Alabama at Birmingham, College of Arts and Sciences, Campbell Hall 415, 1720 2nd Avenue South, Birmingham, Alabama, 35294, USA. epcostas@uab.edu.
authors.forename: Emma
authors.initials: E
authors.lastname: Perez-Costas
authors.affiliation: Division of Pharmacy, College of Pharmacy and Nutrition, University of Saskatchewan, 1B23 Health Sciences Building, 107 Wiggins Road, Saskatoon, SK, S7N 5E5, Canada. erin.fenton@usask.ca.
authors.forename: Erin Y
authors.initials: EY
authors.lastname: Fenton
authors.affiliation: Division of Pharmacy, College of Pharmacy and Nutrition, University of Saskatchewan, 1B23 Health Sciences Building, 107 Wiggins Road, Saskatoon, SK, S7N 5E5, Canada. hector.caruncho@usask.ca.
authors.forename: Hector J
authors.initials: HJ
authors.lastname: Caruncho
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000648:ultrastructure; D001921:Brain / Q000098:blood supply* / Q000378:metabolism* / Q000648:ultrastructure; D002196:Capillaries / Q000378:metabolism* / Q000648:ultrastructure; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010784:Photomicrography; D051381:Rats; D000091042:Reelin Protein; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; D000091042:Reelin Protein; C000717129:Reln protein, rat; D012697:Serine Endopeptidases