Increased sensitivity to N-methyl-D-aspartate receptor-induced excitotoxicity in cerebellar granule cells from interleukin-1 receptor type I-deficient mice.
The effects of chronic exposure to excitatory amino acids (EAAs) were examined in cultured cerebellar granule cells (CGCs) from wild type (WT) and interleukin-1 receptor type I (IL-1RI)-deficient mice. After 8 days in culture, the cells were exposed to 100 microM glutamate or 300 microM N-methyl-D-aspartate (NMDA) for 24 h. Analysis of cell viability, as assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay and phase-contrast microscopy revealed that CGCs from IL-1RI-deficient mice were more vulnerable to EAAs as compared to the WT controls. The results indicate that IL-1RI signalling is important for neuronal survival. The effect of glutamate on the CGCs from IL-1RI-deficient mice was decreased by the non-competitive NMDA-receptor antagonist MK-801, supporting the involvement of NMDA receptors in the glutamate-induced excitotoxicity.
Pelidou
Sigliti Henrietta
SH
Department of Neurochemistry and Neurotoxicology, The Arrhenius Laboratories for Natural Sciences, Stockholm University, SE-106 91, Stockholm, Sweden.
Schultzberg
Marianne
M
Iverfeldt
Kerstin
K
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects / Q000276:immunology; D002525:Cerebellar Cortex / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D004660:Encephalitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D019636:Neurodegenerative Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D017472:Receptors, Interleukin-1 / Q000172:deficiency* / Q000235:genetics; D053573:Receptors, Interleukin-1 Type I; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism*
D018691:Excitatory Amino Acid Antagonists; D009498:Neurotoxins; D017472:Receptors, Interleukin-1; D053573:Receptors, Interleukin-1 Type I; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid