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.
Abdulla
E M
EM
Wellcome Research Laboratories, Beckenham, Kent, United Kingdom.
Campbell
I C
IC
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