Regional regulation of glutamate signaling during cuprizone-induced demyelination in the brain

Azami-Tameh, A. and Clarner, T. and Beyer, C. and Atlasi, M.A. and Hassanzadeh, G. and Naderian, H. (2013) Regional regulation of glutamate signaling during cuprizone-induced demyelination in the brain. Annals of Anatomy, 195 (5). pp. 415-423.

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Abstract

Glutamate excitotoxicity is associated with a wide range of neurodegenerative disorders and also seems to be involved in the pathology of demyelinating disorders such as multiple sclerosis (MS). Cuprizone-induced toxic demyelination shows clear characteristics of MS such as demyelination and axonal damage without the involvement of the innate immune system. In this study, we have evaluated glutamate signaling during cuprizone-induced demyelination in the white and gray matter of mouse brain by studying the expression of ionotropic and metabotropic glutamate-receptors and -transporters by Affymetrix gene array analysis, followed by real-time PCR and western blot analysis. Cellular localization of glutamate transporters was investigated by fluorescence double-labeling experiments. Comparing white and gray matter areas, the expression of glutamate receptors was region-specific. Among NMDA receptor subunits, NR2A was up-regulated in the demyelinated corpus callosum (CC), whereas the metabotropic glutamate receptor mGluR2 was down-regulated in demyelinated gray matter. Glutamate-aspartate transporter (GLAST) co-localizing with GFAP+ astrocytes was increased in both demyelinated CC and telencephalic cortex, whereas Slc1a4 transporter was up-regulated only in CC. Our data indicate that cuprizone treatment affects glutamate-receptors and -transporters differently in gray and white matter brain areas revealing particularly regulation of GLAST and Slc1a4 compared with other genes. This might have an important influence on brain-region selective sensitivity to neurotoxic compounds and the progression of demyelination as has been reported for MS and other demyelinating neurological diseases. © 2013 Elsevier GmbH.

Item Type: Article
Additional Information: cited By 12
Uncontrolled Keywords: cuprizone; excitatory amino acid transporter; glutamate transporter; glutamic acid; ionotropic receptor; metabotropic receptor; metabotropic receptor 2; n methyl dextro aspartic acid receptor; n methyl dextro aspartic acid receptor 2A; neurotoxin; protein Slc1a4; unclassified drug, animal cell; animal experiment; animal model; animal tissue; article; astrocyte; brain cortex; brain region; cellular distribution; controlled study; corpus callosum; demyelinating disease; disease exacerbation; gray matter; male; mouse; multiple sclerosis; neurotoxicity; neurotransmission; nonhuman; nucleotide sequence; protein expression; protein localization; receptor down regulation; receptor upregulation; regulatory mechanism; sensitivity analysis; telencephalon; tissue structure; white matter, AMPA; bovine serum albumin; BSA; CC; central nervous system; CNS; corpus callosum; Cuprizone; Demyelination; EAAT; EAE; ECL; enhanced chemiluminescence; excitatory amino acid transporter; experimental allergic encephalomyelitis; GFAP; GLAST; glial fibrillary acidic protein; GLT; Glutamate receptor; glutamate receptor, ionotropic AMPA; glutamate receptor, metabotropic; glutamate transporter; Glutamate transporter; glutamate-aspartate transporter; Gria; Grm; horseradish peroxidase; HPRT; HRP; hypoxanthine-guanine phosphoribosyltransferase; Iba; IHC; immunohistochemistry; ionized calcium-binding adaptor molecule; MAPK; MBP; metabotropic glutamate receptors; MGluRs; mitogen-activated protein kinase; MOG; MS; multiple sclerosis; myelin basic protein; myelin oligodendrocyte glycoprotein; N-methyl-d-aspartate; nitric oxide; NMDA; NO; PBS; phosphate-buffered saline; PLP; polyvinylidenfluoride; proteolipid protein; PVDF; SDS; SLC; sodium dodecylsulfate; solute carrier; TGF-β1; transforming growth factor-beta 1; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, Amino Acid Transport System X-AG; Animals; Blotting, Western; Brain; Cells, Cultured; Chelating Agents; Corpus Callosum; Cuprizone; Demyelinating Diseases; Fluorescent Antibody Technique; Glutamic Acid; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Multiple Sclerosis; Protein Array Analysis; Real-Time Polymerase Chain Reaction; Receptors, Glutamate; Signal Transduction
Subjects: Anatomy Morphology
Biochemistry, Genetics and Molecular Biology
Divisions: Faculty of Medicine > Basic Sciences > Department of Anatomy
Depositing User: editor . 2
Date Deposited: 03 Mar 2017 15:30
Last Modified: 03 Mar 2017 15:30
URI: http://eprints.kaums.ac.ir/id/eprint/614

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