Effects of L-beta-N-methylamino-L-alanine (L-BMAA) on the cortical cholinergic and glutamatergic systems of the rat.
Neurotoxic properties of L-beta-methylamino-alanine (L-BMAA) after chronic intracerebroventricular (i.c.v.) (500 micrograms/day) administration up to 60 days were investigated in the cerebral cortex of the rat. At day 16, there was a significant decrease in acetylcholinesterase (AChE) activity, 3H-QNB binding, 3H-glutamate (GLU) binding, and 3H-glutamate binding in the presence of quisqualate (QA). Choline acetyltransferase (ChAT) activity and 3H-nicotine binding were increased at day 16; however, ChAT activity decreased below control levels at days 40 and 60. 3H-Nicotine and 3H-AMPA binding were significantly lower than controls at both days 40 and 60. These significant neurochemical differences from unoperated controls were seen in both drug-injected and non-injected sides of the cortex suggesting a generalized cortical damage to glutamatergic and cholinergic systems. In the presence of bicarbonate, L-BMAA inhibited in vitro both glutamate and AMPA binding sites. L-BMAA treatment elicited behavioral changes such as splay, jerking movements, and rigidity. These symptoms were present for a period of at least 6 days after daily administration. After this period, symptoms were gradually attenuated and at day 10 the behavior of the L-BMAA-treated animals was not different from that of Na-bicarbonate injected controls. Our results are interpreted as an activation of quisqualate (AMPA) receptors by L-BMAA involving NMDA as well as non-NMDA receptors.
Rakonczay
Z
Z
Department of Pharmacology, Southern Illinois University, School of Medicine, Springfield 62794.
Matsuoka
Y
Y
Giacobini
E
E
D000110:Acetylcholinesterase / Q000378:metabolism; D000599:Amino Acids, Diamino / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D000087522:Cyanobacteria Toxins; D007051:Ibotenic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects*; D011813:Quinuclidinyl Benzilate; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
D000599:Amino Acids, Diamino; D000087522:Cyanobacteria Toxins; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; C001824:beta-N-methylamino-L-alanine; D007051:Ibotenic Acid; D011813:Quinuclidinyl Benzilate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D016318:Quisqualic Acid; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase