Selective vulnerability of spinal cord motor neurons to non-NMDA toxicity.
We previously reported that alpha-motor neurons in organotypic cultures of rat spinal cord (OTC-SC) are resistant to excitotoxicity induced through NMDA receptors. Here we describe the effects of non-NMDA glutamate receptor agonists kainic acid (KA) and quisqualic acid (QUIS) on motor neurons in OTC-SC. Large ventral horn acetylcholinesterase-positive neurons (VHANs), most of which are motor neurons, were quite sensitive to QUIS and KA toxicity and displayed losses of 95% and 94%, respectively. Small VHANs were reduced by 41% and 61% only. Identical results were obtained in cultures stained for non-phosphorylated neurofilaments. These observations demonstrate that alpha-motor neurons are considerably more sensitive to KA and QUIS than to NMDA toxicity. The proposed excitotoxic mechanism of ALS, therefore, is most likely mediated through non-NMDA glutamate receptors.
Saroff
D
D
Department of Medicine (Neuroscience), Harvard Medical School, Boston, MA, USA.
Delfs
J
J
Kuznetsov
D
D
Geula
C
C
D000110:Acetylcholinesterase / Q000378:metabolism; D000690:Amyotrophic Lateral Sclerosis / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D048429:Cell Size; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology*; D002478:Cells, Cultured; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity; D009046:Motor Neurons / Q000187:drug effects* / Q000473:pathology*; D016900:Neurofilament Proteins / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity*; D016318:Quisqualic Acid / Q000633:toxicity; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology
D018690:Excitatory Amino Acid Agonists; D016900:Neurofilament Proteins; D009498:Neurotoxins; D017470:Receptors, Glutamate; D016318:Quisqualic Acid; D000110:Acetylcholinesterase; D007608:Kainic Acid