CYTOPROTECTIVE ACTIONS OF 2,4-DIMETHOXYBENZYLIDENE ANABASEINE IN DIFFERENTIATED PC12 CELLS AND SEPTAL CHOLINERGIC NEURONS

The potential cytoprotective actions of a novel nicotinic agent 2,4-di methoxybenzilidene anabaseine (DMXB) were investigated in differentiat ed PC12 cells and transected rat septal cholinergic neurons in vivo. I n NCF-differentiated PC12 cells, removal of both NGF and serum led to cell loss, a reduced % of cells expressing neurites, the release of la ctate dehydrogenase, and a decrease in total cellular protein. Cell lo ss was apparent within 24 h, and remained constant between 4-8 days po st-NGF removal. NGF alone (100 ng/ml), DMXB (10 mu M), but not nicotin e (10 mu M), prevented these cell and neurite losses. DMXB-induced cyt oprotection was blocked by 1 mu M mecamylamine. DMXB (1 mg/kg, ip) inj ected twice but not once per day protected cholinesterase-staining sep tal neurons from retrograde degeneration following unilateral fimbrial transections. The twice per day DMXB injection-protocol also decrease d cell roundness among cholinesterase-staining cells in the lesioned s eptal hemisphere compared to saline-injected animals. These studies su ggest that DMXB may exert cytoprotective activity in NGF-sensitive neu ronal populations. (C) 1994 Wiley-Liss, Inc.