Effects of mitochondrial dysfunction on glutamate receptor-mediated neurotoxicity in cultured rat spinal motor neurons

Brain Research
Rie KankiShun Shimohama

Abstract

Glutamate-induced excitotoxicity is implicated as playing a key role in the pathogenesis of amyotrophic lateral sclerosis (ALS), and mitochondrial dysfunction is also found in ALS patients. We investigated the relationship between glutamate excitotoxicity and mitochondrial dysfunction elicited by rotenone (a complex I inhibitor), malonate (a complex II inhibitor), or antimycin (a complex III inhibitor), in primary cultures of the embryonic rat spinal cord. Rotenone and malonate induced relatively selective toxicity against motor neurons as compared to non-motor neurons, whereas antimycin caused non-selective toxicity. The toxicity of rotenone was prevented by a non-N-methyl-D-aspartate (NMDA) receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) but not by an NMDA receptor antagonist, 5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK-801). The toxicity of malonate was blocked by both CNQX and MK-801. The toxicity of antimycin was affected by neither CNQX nor MK-801. When mitochondrial complex I was mildly inhibited by a sub-lethal concentration of rotenone, AMPA-induced motor neuron death was significantly exacerbated. A sub-lethal concentration of malonate exacerbated both NMDA- and ...Continue Reading

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Citations

Jan 11, 2005·Neurotoxicity Research·Gilles J GuilleminBruce J Brew
Aug 16, 2006·Neuro-degenerative Diseases·Gilles J GuilleminBruce J Brew
Mar 17, 2009·Molecular Neurodegeneration·Tania F Gendron, Leonard Petrucelli
Nov 26, 2015·Neuroscience and Biobehavioral Reviews·Alida Spalloni, Patrizia Longone
Sep 28, 2010·Biochemical and Biophysical Research Communications·Maria SimarroPaul Anderson
Feb 24, 2015·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Shui GuanZhanfeng Cui
Jun 7, 2016·Neuropharmacology·Jong-Min LeeGilles J Guillemin
Jul 6, 2016·Neuroscience and Biobehavioral Reviews·Giselli ScainiJoão Quevedo
Dec 10, 2016·Molecular Biology of the Cell·Pamela J YaoMark P Mattson
Jun 29, 2017·Journal of Pineal Research·Almudena CrookeJesús Pintor
Feb 14, 2019·Connective Tissue Research·Ra Jeong KimHyung Bin Park
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Jun 16, 2017·Neural Regeneration Research·Robert B Shultz, Yinghui Zhong

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