Article date: 1991/5/1
PubMed ID: 1653366
Journal name: Journal of neuroscience research (ISSN: 0360-4012)
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.
Author List: Rakonczay Z, Matsuoka Y, Giacobini E
Publication Types: Journal Article; Research Support, Non-U.S. Gov't
Substances mentioned in the article: Amino Acids, Diamino; Receptors, Glutamate; Receptors, Neurotransmitter; beta-N-methylamino-L-alanine; Ibotenic Acid; Quinuclidinyl Benzilate; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Quisqualic Acid; Choline O-Acetyltransferase; Acetylcholinesterase;
Mesh terms: Acetylcholinesterase/metabolism; Amino Acids, Diamino/administration & dosage; Animals; Behavior, Animal/drug effects; Brain Chemistry/drug effects; Cerebral Cortex/drug effects; Choline O-Acetyltransferase/metabolism; Ibotenic Acid/analogs & derivatives; Injections, Intraventricular; Male; Parasympathetic Nervous System/drug effects; Quinuclidinyl Benzilate; Quisqualic Acid; Rats; Rats, Inbred Strains; Receptors, Glutamate; Receptors, Neurotransmitter/drug effects; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid;