Use of neurite outgrowth as an in vitro method of assessing neurotoxicity.
This work shows that the neurotoxic excitatory amino acids beta-N-methylamino alanine, BMAA, and kainate, modulate neurite outgrowth; this was assessed by measuring the levels of two separate neurofilament proteins (68 kD and 160 kD), in a mouse neuroblastoma cell line, (NB41A3). BMAA has been proposed to be the exogenous excitotoxin in Guam disease or amyotrophic lateral sclerosis (ALS/parkinsonian/dementia; Guam ALS-PD). Kainate is a glutamate analogue which causes excitotoxic damage associated with excessive entry of calcium into neurons. The results show that at low doses (10(-9) to 10(-7) M) both BMAA and kainate decrease the concentration of the two neurofilament proteins. However at high doses (10(-6) to 10(-5) M) they cause an apparent accumulation of the neurofilament proteins; the effect is more marked with BMAA. These results support the continued development of an in vitro test for neurotoxicity based on neurite outgrowth.
Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
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Abdulla
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Campbell
D000599:Amino Acids, Diamino / Q000633:toxicity*; D000818:Animals; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D002454:Cell Differentiation; D000087522:Cyanobacteria Toxins; D004797:Enzyme-Linked Immunosorbent Assay; D007608:Kainic Acid / Q000633:toxicity*; D051379:Mice; D016501:Neurites / Q000502:physiology* / Q000648:ultrastructure; D009447:Neuroblastoma; D016900:Neurofilament Proteins / Q000032:analysis / Q000378:metabolism*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects / Q000473:pathology; D009498:Neurotoxins / Q000633:toxicity*; D014407:Tumor Cells, Cultured
D000599:Amino Acids, Diamino; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D000087522:Cyanobacteria Toxins; D016900:Neurofilament Proteins; D009498:Neurotoxins; C001824:beta-N-methylamino-L-alanine; D007608:Kainic Acid