Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Neurosciences, Neurosciences & Neurology, calcium, motor neurons, neurolathyrism, oxidative stress, EXCITOTOXIN BETA-N-OXALYL-L-ALPHA,BETA-DIAMINOPROPIONIC ACID, EXCITATORY AMINO-ACID, LATHYRUS-SATIVUS, AMPA RECEPTORS, SPINAL-CORD, APOPTOSIS, SYSTEM, MOTONEURONS, GLUTATHIONE, INHIBITION, Animals, Cells, Cultured, Lathyrism, Motor Neuron Disease, Motor Neurons, Nerve Degeneration, Oxidative Stress, Rats, beta-Alanine, 1109 Neurosciences, 1702 Cognitive Sciences, Neurology & Neurosurgery, 3209 Neurosciences, 5202 Biological psychology

Abstract:

The excitatory amino acid L-β-N-oxalyl-α,β-diaminopropionic acid (L-β-ODAP) in Lathyrus sativus L. is proposed as the causative agent of the neurodegenerative disease neurolathyrism. We investigated the effect of L-β-ODAP on [Ca2+]i handling, redox homeostasis, and cell death in rat spinal motor neurons. L-β-ODAP and L-glutamate triggered [Ca2+]i transients, which were inhibited by the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor blockers; 2,3-dioxo-6-nitro-1,2,3, 4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide and 1-naphthyl acetylspermine, the latter specifically blocking Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors. In addition, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide, and to a lesser extent 1-naphthyl acetylspermine, protected the neurons against cell death induced by L-β-ODAP or L-glutamate. Methionine and cysteine were also protective against neuronal cell death. We conclude that deregulation of [Ca2+]i homeostasis and oxidative stress contribute to motor neuron cell death in neurolathyrism.