L-BMAA AND KAINATE-INDUCED MODULATION OF NEUROFILAMENT CONCENTRATIONSAS A MEASURE OF NEURITE OUTGROWTH - IMPLICATIONS FOR AN IN-VITRO TESTOF NEUROTOXICITY

This work shows that the neurotoxic excitatory amino acid analogues be ta-N-methyl-L-amino-alanine (L-BMAA) and kainate, modulate neurite out growth. This was assessed indirectly by measuring the levels of two di fferent neurofilament proteins (68 kDa and 160 kDa) in a mouse neurobl astoma cell line (NB41A3). The results of this study show that at low doses (10(-9)-10(-7) m) both L-BMAA and kainate decrease the concentra tion of the two neurofilament proteins but that at high doses (10(-6)- 10(-5) m) they cause an apparent accumulation; the effect is more mark ed with L-BMAA. The sensitivity of the neurofilaments to low doses (10 (-8) M) of the latter suggests that this test may be useful as a gener al in vitro test of neurotoxicity. In addition, these in vitro observa tions may shed light on the formation of the 'neurofibrillary tangles' commonly found in the brains of patients who have had Guam disease an d/or Alzheimer's disease.