Billion-fold difference in the toxic potencies of two excitatory plant amino acids, L-BOAA and L-BMAA: biochemical and morphological studies using mouse brain slices.

Abstract

Plant amino acids beta-N-oxalylamino-L-alanine (L-BOAA, present in Lathyrus sativus) and beta-N-methylamino-L-alanine (L-BMAA, present in Cycas circinalis) have been implicated in the pathogenesis of human neurological disorders lathyrism and amyotrophic lateral sclerosis-Parkinson's dementia complex of Guam (ALS-PD), respectively. In view of the conflicting reports that have emerged on the role of L-BMAA in ALS-PD, we reinvestigated the comparative toxicity of L-BMAA and L-BOAA. We report here the potent toxicity of L-BOAA as examined in an in vitro model consisting of sagittal slices of mouse brain. Incubation of sagittal slices of mouse brain with L-BOAA (1 pM) resulted in significant leakage of lactate dehydrogenase (LDH) and potassium from the slices into the medium. Under similar conditions, L-BMAA-induced LDH leakage from the slices into the medium was observed only at very high concentration of the toxin, namely 1 mM. N-Methyl-D-aspartate (NMDA) receptor antagonists ameliorated the toxic effects of L-BMAA, while non-NMDA receptor antagonists (quinoxalinediones) protected against the toxicity of L-BOAA. Incubation of slices with L-BOAA for 1 h resulted in extensive vacuolation and degeneration of neurons in the thalamus and brain stem, and to a lesser extent in the hippocampus and cerebellar nuclei. The large sized neurons appeared to be affected to a greater extent than the smaller ones. The neurons in other areas of the brain also revealed variable degree of degeneration with swelling of axons and dendrites.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: K S Pai, S K Shankar, V Ravindranath
• Journal: Neuroscience research (Neurosci Res) Vol. 17 Issue 3 Pg. 241-8 (Aug 1993) ISSN: 0168-0102 [Print] Ireland
• PMID: 7901822 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acids, Diamino
• Cyanobacteria Toxins
• Excitatory Amino Acid Antagonists
• Neurotoxins
• Quinoxalines
• beta-N-methylamino-L-alanine
• 2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline
• beta-Alanine
• oxalyldiaminopropionic acid
• Dizocilpine Maleate
• 6-Cyano-7-nitroquinoxaline-2,3-dione
• L-Lactate Dehydrogenase
• Potassium

Topics

• 6-Cyano-7-nitroquinoxaline-2,3-dione
• Amino Acids, Diamino (toxicity)
• Animals
• Brain (anatomy & histology, drug effects, enzymology)
• Brain Chemistry (drug effects)
• Cyanobacteria Toxins
• Dizocilpine Maleate (pharmacology)
• Excitatory Amino Acid Antagonists
• Histocytochemistry
• In Vitro Techniques
• L-Lactate Dehydrogenase (metabolism)
• Mice
• Neurotoxins (toxicity)
• Paraffin Embedding
• Plants (chemistry)
• Potassium (metabolism)
• Quinoxalines (pharmacology)
• beta-Alanine (analogs & derivatives, toxicity)