NEURITE DEGENERATION IN DIFFERENTIATED HUMAN NEUROBLASTOMA-CELLS

We have studied neurite degeneration in differentiated human neuroblas toma (SH-SY5Y) cells. The axonopathy-inducing potency in vitro of caff eine, diazepam, methylmercury chloride (MeHg), triethyltin chloride (T ET) and acrylamide (ACR) was elucidated. After 72 hours of exposure th e neurite degeneration was determined (by morphological quantification ) as well as the total protein content (general cytotoxicity). The con centrations that caused 20% reduction of number of neurites (ND20) for ACR (250 +/- 36 mu M) and TET (0.097 +/- 0.03 mu M) was significantly lower, 63% and 35%, respectively (P less than or equal to 0.005), as compared to corresponding inhibition of general cytotoxicity (IC20) Th e effects of TET on the neurites may be related to the disturbance in Ca2+-signalling, and thus a secondary event. The ND(20)s for caffeine and diazepam, which are compounds without a known neurite degenerative potency in vivo, were higher as compared with the IC20. For MeHg whic h is an extremely cyto- and neurotoxic compound the ND20 was not stati stically different from the IC20, indicating that degeneration of the neurites is not a primary effect. This study indicates that the SH-SY5 Y-neurite degeneration model is useful for the identification of axono pathy-inducing substances. (C) 1998 Elsevier Science Ltd. All rights r eserved.