Cytoprotective actions of 2,4‐dimethoxybenzylidene anabaseine in differentiated PC12 cells and septal cholinergic neurons

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Abstract
The potential cytoprotective actions of a novel nicotinic agent 2,4‐dimethoxybenzilidene anabaseine (DMXB) were investigated in differentiated PC12 cells and transected rat septal cholinergic neurons in vivo. In NGF‐differentiated PC12 cells, removal of both NGF and serum led to cell loss, a reduced % of cells expressing neurites, the release of lactate dehydrogenase, and a decrease in total cellular protein. Cell loss was apparent within 24 h, and remained constant between 4–8 days post‐NGF removal. NGF alone (100 ng/ml), DMXB (10 μM), but not nicotine (10 μM), prevented these cell and neurite losses. DMXB‐induced cytoprotection was blocked by 1 μM mecamylamine. DMXB (1 mg/kg, ip) injected twice but not once per day protected cholinesterase‐staining septal neurons from retrograde degeneration following unilateral fimbrial transections. The twice per day DMXB injection‐protocol also decreased cell roundness among cholinesterase‐staining cells in the lesioned septal hemisphere compared to saline‐injected animals. These studies suggest that DMXB may exert cytoprotective activity in NGF‐sensitive neuronal populations.