ACRYLAMIDE AND 2,5-HEXANEDIONE INDUCE COLLAPSE OF NEUROFILAMENTS IN SH-SY5Y HUMAN NEUROBLASTOMA-CELLS TO FORM PERIKARYAL INCLUSION-BODIES

Neurofilament accumulations are characteristic of a number of neurolog ical conditions including amyotrophic lateral sclerosis, giant axonal neuropathies and several chemically-induced neuropathies. Although the mechanism(s) leading to neurofilament accumulation are unknown, it is possible that similar processes occur both in disease and in chemical ly-induced neuropathies. Understanding the mechanism(s) of chemically- induced neurofilament accumulation, which is more amenable to experime ntal manipulation, may give insight into the neurological diseases the y mimic. We have compared the effects of two chemically-dissimilar neu rotoxins, 2,5-hexanedione and acrylamide, on neurofilaments in the hum an neuroblastoma cell line, SH-SY5Y. Both undifferentiated and differe ntiated SH-SY5Y cells were exposed to 2,5-hexanedione or acrylamide an d changes in cytoskeletal organization examined by immunofluorescence and electron microscopy. Although distinct morphological differences h ave previously been characterized in the neuropathies induced by 2,5-h exanedione and acrylamide in vivo, we have found that bath compounds h ad similar direct effects on neurofilaments in SH-SY5Y cells, inducing formation of perikaryal inclusion bodies. In addition, differentiated SH-SY5Y cells were more sensitive to both 2,5-hexanedione and acrylam ide compared with undifferentiated cells. These similar effects of 2,5 -hexanedione and acrylamide lend further support that a common mechani sm(s) may lead to neurofilament accumulation in these neuropathies. SH -SY5Y cells provide a useful model to investigate further the biochemi cal basis of neurofilament accumulation.