Differential Effect of Acetylcholinesterase on Neuronal and Glial Cells in Culture

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by neuronal loss that involves not only cholinergic systems but most specifically those expressing acetylcholinesterase (AChE) (1). Along with neuronal death there is a gliosis reaction. AChE accumulates in senile plaques, which are strongly associated with the neuronal degeneration, in this context, AChE could have a toxic effect on brain cells that could be associated with neuronal degeneration (2). We have reported previously that AChE may be toxic to neuronal and glial-like cell lines in culture, that the toxicity of AChE is concentration and time-dependent and that is independent of its catalytic activity (3). Here we show that AChE is toxic to neuronal cells but not to glial cells in primary cultures obtained from embryonic avian retina (E8). We took advantage of retina cultured cells because they have cholinergic neurons with high levels of AChE expression and because it is also possible to have neuronal and glial cells in the same culture. Cell cultures containing both neurons and glia incubated with AChE purified from bovine brain showed that neuronal cells were sensitive to AChE toxicity however no effect was observed on glial cells (Muller cells) as can be seen by the conserved capacity of glial cells to reduce MTT. The differential effect of AChE on neuronal and glial cells was also shown by the TUNEL technique which reveals DNA fragmentation in situ, a hallmark of apoptotic cell death, showing that neurons exposed to AChE undergo apoptosis however glial cells remains intact. These difference in sensitivity of neuronal and glial cells to the toxic effect of AChE supports the idea that AChE may have a role in the neurodegeneration that occurs in AD where there are a localized accumulation of AChE in the senile plaques.