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.
Chang
Y C
YC
Institute of Life Science, National Tsing-Hua University, Hsinchu, Taiwan.
Chiu
S J
SJ
Kao
K P
KP
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000378:metabolism*; D000087522:Cyanobacteria Toxins; D004338:Drug Combinations; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000378:metabolism*; D013570:Synaptic Membranes / Q000378:metabolism; D015091:beta-Alanine / Q000031:analogs & derivatives / Q000494:pharmacology
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D004338:Drug Combinations; D009498:Neurotoxins; D017470:Receptors, Glutamate; C001824:beta-N-methylamino-L-alanine; D015091:beta-Alanine; C100126:oxalyldiaminopropionic acid; D015763:2-Amino-5-phosphonovalerate