Biochemical and morphological effects of fumonisin B-1 on primary culturesof rat cerebrum

Chronic dietary consumption of the mycotoxin fumonisin B-1 (FB1) is associa ted with leukoencephalomalacia and neuronal degeneration, but identificatio n of the cellular mechanisms underlying this neurotoxicity is difficult due to concurrent adverse systemic changes. For this reason, the present inves tigation used an in vitro approach to assess the short-term consequences of direct FB1 (0.5-75 mu M) exposure on astrocytes and oligodendrocytes in pr imary cultures of rat cerebrum. Beginning at 5 days in vitro, the cultures were exposed to FB1 at five concentrations (0.5-75 mu M), and the cultures were evaluated at 10 and 15 days in vitro. The levels of the sphingolipid-a ssociated constituents sphingosine and sphinganine were determined with a h igh-performance liquid chromatography. Relative to untreated cultures, expo sure to FB1 diminished the levels of sphingosine at 15 days in vitro, where as FB1-exposed cultures showed significantly increased sphinganine levels a nd sphinganine/sphingosine ratios. In addition to these changes in sphingol ipid constituents, FB1-exposed (0.5-75 mu M) cultures exhibited a two-fold increase in the number of process-bearing cells by 15 days in vitro. Also, the activity of 2',3'-cyclic nucleotide 3'-phosphohydrolase, an enzyme asso ciated with myelin and oligodendrocytes, was increased in FB1-treated cultu res. This study suggests that shortterm exposure to FB1 may modify the prol iferation or differentiation of glial cells. (C) 2000 Elsevier Science Inc. All rights reserved.