The effect of acetylcholinesterase on outgrowth of dopaminergic neurons in organotypic slice culture of rat mid-brain

Abstract

This study has investigated the possibility that acetylcholinesterase could play a non-classical role as an adhesion factor or growth factor in the development of dopaminergic neurons in organotypic slice culture of postnatal day 1 rats. When the culture medium was supplemented with acetylcholinesterase (3 U/ml), outgrowth of tyrosine hydroxylase-immunoreactive neurites was significantly enhanced. Addition of a specific inhibitor of acetylcholinesterase, BW284c51, caused a decrease in the number of tyrosine hydroxylase neurons and a reduction in the cell body size and extent of neurite outgrowth of remaining neurons. However, echothiophate which also inhibits AChE activity, did not produce these effects. Therefore acetylcholinesterase could act as a growth enhancing factor for dopaminergic neurons, and disruption of an as yet unidentified site on the acetylcholinesterase molecule by BW284c51 could decrease the survival and outgrowth of these neurons.

Dose-related gene expression changes in forebrain following acute, low-level chlorpyrifos exposure in neonatal rats

“…The classic mechanism of acute neurotoxicity of OPs is initiated by inhibition of the enzyme acetylcholinesterase (AChE), leading to accumulation of the neurotransmitter acetylcholine and resulting cholinergic signs of toxicity (reviewed in Mileson et al, 1998). A number of studies suggest that inhibition of AChE during nervous system development could disrupt neurodevelopmental outcome (Jones et al, 1995; Koenigsberger et al, 1997; Sternfeld et al, 1998; Das and Barone, 1999; Bigbee et al, 2000: Howard et al, 2005; Paranaou and Layer, 2008). Moreover, some OPs can interact with other non-acetylcholinesterase macromolecules to potentially influence nervous system function and/or neurodevelopment (Pope, 1999; Casida and Quistad, 2005; Pope et al, 2005).…”

Acetylcholinesterase-transgenic mice display embryonic modulations in spinal cord choline acetyltransferase and neurexin Iβ gene expression followed by late-onset neuromotor deterioration

“…Accumulated and compelling cell culture evidence increasingly points to noncatalytic morphogenic roles for acetylcholinesterase (AChE), the enzyme known for its function in terminating neurotransmission at cholinergic synapses by hydrolysis of acetylcholine (ACh) (1)(2)(3). At the in vivo milieu, we reported a morphogenic activity for overexpressed human AChE in developing amphibian neuromuscular junctions (NMJs) (4,5).…”

Early appearance of acetylcholinergic, serotoninergic, and peptidergic neurons and fibers in the developing human central nervous system

“…The extensive presence of AChE at non-cholinergic sites suggests a non-catalytic function for this molecule. During development of the nervous system, it has already been shown AChE is a neurite growth factor in the embryonic neurons (Holmes et al, 1997;Jones et al, 1995;Layer, 1991;Layer et al, 1993;Robertson, 1987Robertson, , 1991Srivatsan and Peretz, 1997). Neurite growth in culture was inhibited by AChE inhibitors (Dupree and Bigbee, 1996;Layer et al, 1993).…”