Selective degeneration of cerebellar cortical neurons caused by cycad neurotoxin, L-beta-methylaminoalanine (L-BMAA), in rats.
Both the racemate and the L-form of BMAA (beta-methylaminoalanine), when injected intraperitoneally into young rats, produced acute signs of cerebellar dysfunction and degeneration of cerebellar stellate, basket, Purkinje and Golgi cells, but not granule cells. Degenerative changes were also occasionally seen in cerebellar roof nuclei which may be secondary in nature. No other changes were found in the remainder of the central nervous system. The doses of the L-form of BMAA producing these changes were from 6 to 14 mumols/g body weight, i.e. the lower and upper levels of the dose range used by Vega and Bell (1967) and equivalent to 75 and 183 mg/rat. Doses of 1 to 4 mg/g body weight of the racemate were given to young rats less than 100 g in weight, but no changes were apparent after daily doses of the racemate of 0.5 mg/g body weight. Damage to cerebellar neurons is considered to be the result of excitotoxic activity. All cells showing degeneration are GABAergic, although not all are known to possess N-methyl-D-aspartate (NMDA) receptors. The present finding of selective cerebellar neuron damage may not conflict with the earlier findings of others, but our results suggest that L-BMAA has unusual glutamate receptor binding properties.
Seawright
A A
AA
Department of Veterinary Pathology and Public Health, University of Queensland, Brisbane, Australia.
Brown
A W
AW
Nolan
C C
CC
Cavanagh
J B
JB
D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D002525:Cerebellar Cortex / Q000166:cytology / Q000187:drug effects*; D000087522:Cyanobacteria Toxins; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure; D009498:Neurotoxins / Q000494:pharmacology*; D010947:Plants, Toxic; D051381:Rats; D011919:Rats, Inbred Strains; D013237:Stereoisomerism; D013997:Time Factors
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D009498:Neurotoxins; C001824:beta-N-methylamino-L-alanine