Discovery and partial characterization of primate motor-system toxins.

P. S. Spencer, J. Hugon, A. Ludolph, P. B. Nunn, S. M. Ross, D. N. Roy, H. H. Schaumburg

Research output: Contribution to journalArticle

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Abstract

beta-N-Oxalylamino-L-alanine (BOAA) and beta-N-methylamino-L-alanine (BMAA) are chemically related excitant amino acids isolated from the seed of Lathyrus sativus (BOAA) and Cycas circinalis (BMAA), consumption of which has been linked to lathyrism (an upper motor neuron disorder) and Guam amyotrophic lateral sclerosis (ALS), respectively. Both diseases are associated with degeneration of motor neurons. Experimentally, single doses of BOAA or BMAA induce seizures in neonatal mice and postsynaptic neuronal oedema and degeneration in explants of mouse spinal cord and frontal cortex. Preliminary studies show that these behavioural and pathological effects are differentially blocked by glutamate-receptor antagonists. In macaques, several weeks of daily oral doses of BOAA produce clinical and electrophysiological signs of corticospinal dysfunction identical to those seen in comparably well-nourished animals receiving a fortified diet based on seed of Lathyrus sativus. By contrast, comparable oral dosing with BMAA precipitates tremor and weakness, bradykinesia and behavioural changes, with conduction deficits in the principal motor pathway. BOAA and BMAA (or a metabolite thereof) are the first members of the excitotoxin family to have been shown to possess chronic motor-system toxic potential. These observations provide a rational basis for searching for comparable endogenous neurotoxins in sporadic and inherited forms of human motor neuron disease.

Original languageEnglish (US)
Pages (from-to)221-238
Number of pages18
JournalCiba Foundation symposium
Volume126
StatePublished - 1987
Externally publishedYes

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Primates
Lathyrus
Neurotoxins
Motor Neurons
Seeds
Cycas
Lathyrism
Guam
Efferent Pathways
Excitatory Amino Acid Antagonists
Hypokinesia
Motor Neuron Disease
Poisons
Amyotrophic Lateral Sclerosis
Macaca
Frontal Lobe
Tremor
Edema
Spinal Cord
Seizures

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Spencer, P. S., Hugon, J., Ludolph, A., Nunn, P. B., Ross, S. M., Roy, D. N., & Schaumburg, H. H. (1987). Discovery and partial characterization of primate motor-system toxins. Ciba Foundation symposium, 126, 221-238.

Discovery and partial characterization of primate motor-system toxins. / Spencer, P. S.; Hugon, J.; Ludolph, A.; Nunn, P. B.; Ross, S. M.; Roy, D. N.; Schaumburg, H. H.

In: Ciba Foundation symposium, Vol. 126, 1987, p. 221-238.

Research output: Contribution to journalArticle

Spencer, PS, Hugon, J, Ludolph, A, Nunn, PB, Ross, SM, Roy, DN & Schaumburg, HH 1987, 'Discovery and partial characterization of primate motor-system toxins.', Ciba Foundation symposium, vol. 126, pp. 221-238.
Spencer PS, Hugon J, Ludolph A, Nunn PB, Ross SM, Roy DN et al. Discovery and partial characterization of primate motor-system toxins. Ciba Foundation symposium. 1987;126:221-238.
Spencer, P. S. ; Hugon, J. ; Ludolph, A. ; Nunn, P. B. ; Ross, S. M. ; Roy, D. N. ; Schaumburg, H. H. / Discovery and partial characterization of primate motor-system toxins. In: Ciba Foundation symposium. 1987 ; Vol. 126. pp. 221-238.
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