Schwann cells exhibit excitotoxicity consistent with release of NMDA receptor agonists.
Neurodegenerative effects of Schwann cells transplanted into the central nervous system have been observed previously. We report here that conditioned medium from Schwann cell cultures exhibit degenerative influences on hippocampal neurons. Aliquots of Schwann cell-conditioned medium compromised the morphologic integrity of the neurons, markedly elevated their intracellular calcium concentrations, and decreased their viability. The degenerative effects of Schwann cell medium on neuronal morphology and viability were blocked by N-methyl-D-aspartate (NMDA) receptor antagonists D-(-)-2-amino-5-phosphonopentanoic acid (D-APV) and 5,7-dicholorokynurenic acid (DCKA). Glutamate was detected in Schwann cell-conditioned medium at a concentration on the order of 10(-5) M. D-Amino acid oxidase (DAAOx) also attenuated the neurotoxicity exhibited by Schwann cells. These data suggest that Schwann cells release biologically relevant concentrations of excitotoxins that include glutamate and D-serine.
Wu
Sheng-Zhou
SZ
Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, USA.
Jiang
Shujun
S
Sims
Terry J
TJ
Barger
Steven W
SW
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000633:toxicity; D003605:D-Amino-Acid Oxidase / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005455:Fluorescent Antibody Technique / Q000379:methods; D018698:Glutamic Acid / Q000378:metabolism / Q000633:toxicity*; D006624:Hippocampus / Q000166:cytology*; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists*; D012583:Schwann Cells / Q000737:chemistry* / Q000378:metabolism; D013778:Tetrazolium Salts; D013844:Thiazoles; D013997:Time Factors
D017077:Culture Media, Conditioned; D018691:Excitatory Amino Acid Antagonists; C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D013778:Tetrazolium Salts; D013844:Thiazoles; D018698:Glutamic Acid; D015763:2-Amino-5-phosphonovalerate; D003605:D-Amino-Acid Oxidase; C022616:thiazolyl blue; D007736:Kynurenic Acid; D002118:Calcium; C066192:5,7-dichlorokynurenic acid