Cell culture evidence for neuronal degeneration in amyotrophic lateral sclerosis being linked to glutamate AMPA/kainate receptors.
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons. Glutamate, a potent central-nervous-system toxin, has been proposed as one possible factor in this motoneuron disease. Serum from patients with ALS is known to be toxic when added to neurons in culture. We report on the toxicity to rat neurons in culture of cerebrospinal fluid (CSF) from patients with ALS. CSF were obtained from 10 ALS patients, 10 neurological controls, and 10 other controls. ALS CSF was added at dilutions of 50%, 20%, or 10% and neuron survival was assessed after 24 h. The neuroprotective effects of antagonists to two glutamate receptors were also assessed. ALS CSF was significantly neurotoxic, with a neuronal survival rate of only 47% compared with 80% or so for control CSF. This neurotoxicity was blocked by CNQX, an antagonist to the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate receptor but not by two N-methyl-D-aspartate (NMDA) antagonists. ALS CSF contains a specific neurotoxic factor which is AMPA/kainate-like which could have a role in the neuronal degeneration of this disease.
Couratier
P
P
Cell Neurobiology Unit, Faculty of Medicine, Limoges, France.
Hugon
J
J
Sindou
P
P
Vallat
J M
JM
Dumas
M
M
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000368:Aged; D000596:Amino Acids / Q000494:pharmacology; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008875:Middle Aged; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology*; D009410:Nerve Degeneration / Q000187:drug effects / Q000502:physiology*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D018091:Receptors, AMPA; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D018092:Kainic Acid Receptors
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000596:Amino Acids; D016291:Dizocilpine Maleate; D011810:Quinoxalines; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D018092:Kainic Acid Receptors; C031231:2-amino-7-phosphonoheptanoic acid