RETARDATION OF NEURITIC OUTGROWTH AND CYTOSKELETAL CHANGES ACCOMPANY ACETYLCHOLINESTERASE INHIBITOR TREATMENT IN CULTURED RAT DORSAL-ROOT GANGLION NEURONS

Over the past two decades acetylcholinesterase (AChE) has been shown t o be present in numerous non-cholinergic and non-cholinoceptive tissue s, Interestingly, transient expression of AChE in developing nervous t issue corresponds temporally with neuronal migration and neuritic outg rowth, This observation has led our laboratory to investigate a possib le novel, noncholinergic role for AChE in the development of the nervo us system, In a previous study, we demonstrated that the activity of A ChE in cultured dorsal root ganglion neurons (DRGN) can be modulated b y the substratum, In our current study, we have examined the effects o f AChE inhibitor treatment on neuritic outgrowth on the highly permiss ive substratum Matrigel Trademark and the less permissive substratum C ollagen Type I, DRGN received serial dilutions of the AChE-specific in hibitor 1,5-bis-(4-allyldimethylammoniumphenyl) pentan-3-one dibromide (BW284c51) ranging from 10(-4) to 10(-7) M. Results showed that neuri tic outgrowth was significantly reduced in DRGN grown on Matrigel Trad emark at 10(-5) and 10(-4) M BW284c51, while outgrowth on Collagen Typ e I was significantly reduced at 10(-6), 10(-5), and 10(-4) M concentr ations of BW284c51, Inhibitor treatment did not affect cell survival a nd neuritic outgrowth from BW284c51-treated cells recovered to control levels after removal of the inhibitor from the medium, In addition, m assive spiraling accumulations of 10 nm filaments were observed in the cell bodies of treated neurons, which resemble neurofibrillary inclus ions observed in neuropathological diseases such as Pick's disease, Th is study demonstrates that AChE inhibitor treatment retards neuritic o utgrowth and neuronal migration of cultured DRGN which is accompanied by cytoskeletal abnormalities in the cell body, These data further sug gest a novel, non-cholinergic role for AChE in neural development and regeneration. (C) 1991 Wiley-Liss, Inc.