beta-N-methylamino-L-alanine (L-BMAA) decreases brain glutamate receptor number and induces behavioral changes in rats.

Rats receiving intracerebroventricular administration of 10 nanomoles of L-BMAA (beta-N-methylamino-L-alanine) were found to grow more slowly and contain less brain L-(3H) glutamate binding sites than rats receiving injection of phosphate-buffered saline (PBS). It was also noticed that rats receiving L-BMAA injection inevitably developed a characteristic behavioral pattern, including loss of mobility and keeping their heads in a tilted position with occasional side to side movement. This unique behavioral pattern was not observed in rats receiving injection of PBS. Rats receiving injection of beta-N-oxalylamino-L-alanine, another toxic plant amino acid, showed a decrease in brain L-(3H) glutamate binding sites, however, without the characteristic behavioral change as induced by L-BMAA. It was further found that rats receiving injection of L-BMAA plus 2-amino-5-phosphonovalerate were similar to those injected with PBS with respect to their L-(3H) glutamate binding activity and behavioral pattern. Results obtained here show that L-BMAA at nanomole level is able to elicit neurotoxic effects on rats and that these toxic effects are mediated by N-methyl-D-asparate-subtype L-glutamate receptors. The results also show that a decrease in glutamate receptor number results from L-BMAA treatment, suggesting an involvement of altered glutamate receptor level in the manifestation of L-BMAA neurotoxicity.