title: Ionotropic glutamate receptor expression in human white matter.
abstract: Glutamate is the key excitatory neurotransmitter of the central nervous system (CNS). Its role in human grey matter transmission is well understood, but this is less clear in white matter (WM). Ionotropic glutamate receptors (iGluR) are found on both neuronal cell bodies and glia as well as on myelinated axons in rodents, and rodent WM tissue is capable of glutamate release. Thus, rodent WM expresses many of the components of the traditional grey matter neuron-to-neuron synapse, but to date this has not been shown for human WM. We demonstrate the presence of iGluRs in human WM by immunofluorescence employing high-resolution spectral confocal imaging. We found that the obligatory N-methyl-d-aspartic acid (NMDA) receptor subunit GluN1 and the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA4 co-localized with myelin, oligodendroglial cell bodies and processes. Additionally, GluA4 colocalized with axons, often in distinct clusters. These findings may explain why human WM is vulnerable to excitotoxic events following acute insults such as stroke and traumatic brain injury and in more chronic inflammatory conditions such as multiple sclerosis (MS). Further exploration of human WM glutamate signalling could pave the way for developing future therapies modulating the glutamate-mediated damage in these and other CNS disorders.
authors.affiliation: Hotchkiss Brain Institute, Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, T2 N 4N1, Canada.
authors.forename: Pia Crone
authors.initials: PC
authors.lastname: Christensen
authors.affiliation: ICORD, (International Collaboration on Repair Discoveries), Department of Pathology and Laboratory Medicine, University of British Columbia, Canada.
authors.forename: Zahra
authors.initials: Z
authors.lastname: Samadi-Bahrami
authors.affiliation: ICORD, (International Collaboration on Repair Discoveries), Department of Pathology and Laboratory Medicine, University of British Columbia, Canada.
authors.forename: Vlady
authors.initials: V
authors.lastname: Pavlov
authors.affiliation: Hotchkiss Brain Institute, Department of Clinical Neuroscience, University of Calgary, Calgary, Alberta, T2 N 4N1, Canada. Electronic address: pstys@ucalgary.ca.
authors.forename: Peter K
authors.initials: PK
authors.lastname: Stys
authors.affiliation: ICORD, (International Collaboration on Repair Discoveries), Department of Pathology and Laboratory Medicine, University of British Columbia, Canada.
authors.forename: G R Wayne
authors.initials: GRW
authors.lastname: Moore
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D001369:Axons / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D018613:Microscopy, Confocal; D008875:Middle Aged; D009186:Myelin Sheath / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009836:Oligodendroglia / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D058468:Receptors, Ionotropic Glutamate / Q000378:metabolism*; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D066127:White Matter / Q000378:metabolism*
chemical_list: C485668:GRIN1 protein, human; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D058468:Receptors, Ionotropic Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; C104724:glutamate receptor ionotropic, AMPA 4
keywords: AMPA; CNS; Ionotropic glutamate receptor; NMDA; Spectral confocal microscopy; White matter