l-BMAA and kainate-induced modulation of neurofilament concentrations as a measure of neurite outgrowth: Implications for an in vitro test of neurotoxicity.
This work shows that the neurotoxic excitatory amino acid analogues beta-N-methyl-l-amino-alanine (l-BMAA) and kainate, modulate neurite outgrowth. This was assessed indirectly by measuring the levels of two different neurofilament proteins (68 kDa and 160 kDa) in a mouse neuroblastoma 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 concentration of the two neurofilament proteins but that at high doses (10(-6)-10(-5)m) they cause an apparent accumulation; the effect is more marked 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 general in vitro test of neurotoxicity. In addition, these in vitro observations may shed light on the formation of the 'neurofibrillary tangles' commonly found in the brains of patients who have had Guam disease and/or Alzheimer's disease.
Abdulla
E M
EM
Wellcome Research Laboratories, Beckenham, Kent, UK; Institute of Psychiatry, London, UK.
Campbell
I C
IC