Acute excitotoxicity in chick retina caused by the unusual amino acids BOAA and BMAA: Effects of MK-801 and kynurenate

Zeevalk, Gail D.; Nicklas, William J.

doi:10.1016/0304-3940(89)90093-1

Cited by 48 publications

(12 citation statements)

References 16 publications

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“…Because Glu acts at both NMDA and nonNMDA receptors, it is not surprising that both CNQX and MK-801 were required to protect against Glu-induced damage. MK-801 effectively blocked damage by NMDA, whereas the protective action of CNQX against the other EAA agonists is consistent with available evidence identifying them as nonNMDA receptor agonists, except for BMAA, which has also been described as an NMDA agonist [20,51). Mixed receptor specificity for BMAA would be consistent with the observations of Weiss and colleagues, who first described BMAA as an NMDA agonist [30], then reported that it behaves as a nonNMDA agonist at lower, presumably more physiologically relevant concentrations [52].…”

Section: Discussionsupporting

confidence: 81%

Excitotoxicity in the embryonic chick spinal cord

Stewart

Olney

Pathikonda

et al. 1991

Annals of Neurology

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Recent evidence implicates excitatory amino acids (EAAs), acting as excitotoxic agents, in the pathogenesis of neurological disorders involving the spinal cord. In this study, we used the chick embryo spinal cord as an in vitro model for studying the sensitivity of spinal neurons to the excitotoxic effects of EAA agonists. Compounds tested include the prototypic receptor-specific agonists, N-methyl-D-aspartate (NMDA), quisqualic acid (Quis), and kainic acid (KA), and the plant-derived excitotoxic food poisons, beta-N-oxalylamino-L-alanine, beta-N-methylamino-L-alanine, and domoic acid. Each agonist induced concentration-dependent acute degeneration of neurons distributed throughout the spinal cord. These cytopathological changes consisted of acute edematous degeneration of dendrosomal structures in the dorsal horn and intermediate zone, and dark cell changes with intracytoplasmic vacuolization of motor neurons; this damage is identical to that induced by excitotoxin agonists in other regions of the central nervous system. The NMDA receptor-specific antagonist MK-801 completely blocked toxicity of NMDA, and the nonNMDA antagonist CNQX preferentially blocked the toxicity of Quis- and KA-type agonists in the spinal cord. Our findings suggest that (1) the majority of spinal neurons have all three subtypes of EAA receptors, making them acutely vulnerable to excitotoxin exposure; and (2) EAA antagonists are effective in preventing excitotoxin-induced damage of the spinal cord.

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Section: Discussionsupporting

confidence: 81%

Excitotoxicity in the embryonic chick spinal cord

Stewart

Olney

Pathikonda

et al. 1991

Annals of Neurology

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“…Previous studies have found that BMAA is neurotoxic both in vivo and in vitro Weiss and Choi, 1988;Weiss et al, 1989;Zeevalk and Nicklas, 1989), but that induction of neuronal death by BMAA requires high concentrations. We repeated these studies in cortical cultures and found similar results, with no significant toxicity occurring until a BMAA concentration of 1 mM (Figure 1).…”

Section: Low Concentration Of Bmaa Potentiates Effects Of Other Neuromentioning

confidence: 97%

β-N-methylamino-l-alanine enhances neurotoxicity through multiple mechanisms

Lobner

Piana

Salous

et al. 2007

Neurobiology of Disease

236

136

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The idea that the environmental toxin β-N-methylamino-L-alanine (BMAA) is involved in neurodegenerative diseases on Guam has risen and fallen over the years. The theory has gained greater interest with recent reports that BMAA is biomagnified, is widely distributed around the planet, and is present in the brains of Alzheimer's patients in Canada. We provide two important new findings. First, we show that BMAA at concentrations as low as 10 µM can potentiate neuronal injury induced by other insults. This is the first evidence that BMAA at concentrations below the mM range can enhance death of cortical neurons and illustrates potential synergistic effects of environmental toxins with underlying neurological conditions. Second, we show that the mechanism of BMAA toxicity is three fold: it is an agonist for NMDA and mGluR5 receptors, and induces oxidative stress. The results provide further support for the hypothesis that BMAA plays a role in neurodegenerative diseases.

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“…To verify that the cells had matured into a more neuron-like phenotype during differentiation, the expression of the neuronal markers βIII-tubulin and microtubule-associated protein-2 (MAP2) (Zeevalk and Nicklas 1989; Kovalevich and Langford 2013), was examined by immunocytochemistry. Cells were cultured and differentiated on polylysine coated glass in 24-well plates as mentioned above.…”

Section: Methodsmentioning

confidence: 99%

“…Previous studies demonstrated that BMAA is a mixed glutamate receptor agonist that can induce excitotoxicity in primary neurons in vitro and in vivo (Weiss et al 1989; Zeevalk and Nicklas 1989; Chiu et al 2012) but BMAA is also suggested to induce neurotoxicity through other mechanisms such as oxidative stress (Lobner et al 2014). Recent studies have demonstrated enrichment of proteins implicated in protein aggregation, and an increased protein ubiquitination in the adult hippocampus following neonatal administration suggesting BMAA-induced perturbations of cellular protein homeostasis (Karlsson et al 2014).…”

Section: Introductionmentioning

confidence: 99%

β-N-Methylamino-l-alanine (BMAA) perturbs alanine, aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling

et al. 2017

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β-Methylamino-l-alanine (BMAA) is a non-proteinogenic amino acid that induces long-term cognitive deficits, as well as an increased neurodegeneration and intracellular fibril formation in the hippocampus of adult rodents following short-time neonatal exposure and in vervet monkey brain following long-term exposure. It has also been proposed to be involved in the etiology of neurodegenerative disease in humans. The aim of this study was to identify metabolic effects not related to excitotoxicity or oxidative stress in human neuroblastoma SH-SY5Y cells. The effects of BMAA (50, 250, 1000 µM) for 24 h on cells differentiated with retinoic acid were studied. Samples were analyzed using LC–MS and NMR spectroscopy to detect altered intracellular polar metabolites. The analysis performed, followed by multivariate pattern recognition techniques, revealed significant perturbations in protein biosynthesis, amino acid metabolism pathways and citrate cycle. Of specific interest were the BMAA-induced alterations in alanine, aspartate and glutamate metabolism and as well as alterations in various neurotransmitters/neuromodulators such as GABA and taurine. The results indicate that BMAA can interfere with metabolic pathways involved in neurotransmission in human neuroblastoma cells.

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Acute excitotoxicity in chick retina caused by the unusual amino acids BOAA and BMAA: Effects of MK-801 and kynurenate

Cited by 48 publications

References 16 publications

Excitotoxicity in the embryonic chick spinal cord

Excitotoxicity in the embryonic chick spinal cord

β-N-methylamino-l-alanine enhances neurotoxicity through multiple mechanisms

β-N-Methylamino-l-alanine (BMAA) perturbs alanine, aspartate and glutamate metabolism pathways in human neuroblastoma cells as determined by metabolic profiling

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