Effects of L-β-N-methylamino-L-alanine (L-BMAA) on the cortical cholinergic and glutamatergic systems of the rat

✍ Scribed by Z. Rakonczay; Y. Matsuoka; Dr. E. Giacobini

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 577 KB
• Volume: 29
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.490290114

✦ Synopsis

Neurotoxic properties of L-p-methylamino-alanine (L-BMAA) after chronic intracerebroventricular (i.c.v.) (500 pgiday) 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 glu tamatergic 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.