title: Cannabinoid receptor CB2 is expressed on vascular cells, but not astroglial cells in the post-mortem human Huntington's disease brain.
abstract: Huntington's disease (HD) is an inherited neurological disease with motor, cognitive and psychiatric symptoms. Characterised by neuronal degeneration, HD pathology is initially apparent in the striatum and cortex. Considerable research has recently suggested that the neurological immune response apparent in brain injury and disease may provide a valuable therapeutic target. Cannabinoid CB2 receptors are localised and up-regulated on a number of peripheral immune cell types following inflammation and injury. However, their cellular location within the human brain during inflammation has not been well characterised. The present study shows CB2 is expressed in human post-mortem striatum in HD. Quantification revealed a trend towards an increase in CB2 staining with disease, but no significant difference was measured compared to neurologically normal controls. In HD striatal tissue, there is an up-regulation of the brains' resident immune cells, with a significant increase in GFAP-positive astrocyte staining at both grade 1 (685±118%) and grade 3 (1145±163%) and Iba1-positive microglia at grade 1 (299±27%) but not grade 3 (119±48%), compared to neurologically normal controls. Both cell types exhibit irregular cell morphology, particularly at higher grades. Using double-labelled immunohistochemistry CB2 receptors are demonstrated not to be expressed on microglia or astrocytes and instead appear to be localised on CD31-positive blood vessel endothelium and vascular smooth muscle. Co-expression analysis suggests that CB2 may be more highly expressed on CD31 positive cells in HD brains than in control brains. Contrasting with evidence from rodent studies suggesting CB2 glial cell localisation, our observation that CB2 is present on blood vessel cells, with increased CD31 co-localisation in HD may represent a new context for CB2 therapeutic approaches to neurodegenerative diseases.
authors: Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland, New Zealand; Medical Research Council Anatomical Neuropharmacology Unit, University of Oxford, Mansfield Rd, Oxford OX13TH, United Kingdom.
authors: Megan J
authors: MJ
authors: Dowie
authors: Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors: Natasha L
authors: NL
authors: Grimsey
authors: Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors: Therri
authors: T
authors: Hoffman
authors: Department of Anatomy with Radiology, Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland, New Zealand.
authors: Richard L M
authors: RL
authors: Faull
authors: Department of Pharmacology and Clinical Pharmacology, Centre for Brain Research, University of Auckland, Private Bag 92019, Auckland, New Zealand. Electronic address: m.glass@auckland.ac.nz.
authors: Michelle
authors: M
authors: Glass
mesh_terms: D000328:Adult; D000368:Aged; D001253:Astrocytes / Q000378:metabolism; D001344:Autopsy; D003342:Corpus Striatum / Q000378:metabolism* / Q000473:pathology; D042783:Endothelial Cells / Q000378:metabolism*; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D043885:Receptor, Cannabinoid, CB2 / Q000096:biosynthesis*
chemical_list: C588309:CNR2 protein, human; D043885:Receptor, Cannabinoid, CB2
keywords: Blood–brain-barrier; Gliosis; Inflammation; Neurodegeneration